Jeremy Hunt has insisted doctors are getting a "fair deal" as he described the latest strike as "very damaging".
The Health Secretary said the last remaining issue to be resolved with the British Medical Association (BMA) related to pay on Saturdays.
And he insisted there had been "no rejection of any proposals and plans" that would deal with the "weekend effect" of more patients dying at weekends.
His comments come as thousands of junior doctors are staging a 24-hour strike across England - covering more than 160 picket lines - in a row over a new contract.
Mr Hunt told the BBC: "The job of health secretary is to do the right thing for patients and we have now had eight studies in the last five years that have shown that mortality rates at weekends are higher than they should be. And my job is to do something about that."
He added: "I think it's a good deal, it's a fair deal."
Asked if the Government had rejected a cost-neutral BMA offer that would have seen doctors' basic pay rise by about half the 11% offered by ministers in return for Saturday not being treated as a normal working day, Mr Hunt said: "There has been no rejection of any proposals and plans that would deal with this weekend effect that is of such concern to patients and the public."
The BMA has confirmed it made such an offer and said it was blocked by the Government.
Mr Hunt went on to describe the industrial action as "very damaging" and said it was "important" to say that 43% of junior doctors had turned up to work.
"So the turnout for the strike has been slightly lower than before" he said.
During the last strike in January, Mr Hunt said "nearly 40%" of junior doctors had turned up to work, although it later emerged the figure included those working in urgent and emergency care, who had been asked not to strike by the BMA.
Junior doctors covering urgent and emergency care have again been asked not to strike. It is unclear if Mr Hunt's latest figures include these doctors.
Dr Johann Malawana, chairman of the BMA's junior doctor committee, said: "With thousands of junior doctors attending more than 160 pickets and 'meet the doctor' events across England, today's action is a resounding rejection of the Government's threat to impose an unfair contract, in which junior doctors have no confidence.
"Junior doctors already work around the clock, seven days a week and they do so under their existing contract. If the Government want more seven-day services then, quite simply, they need more doctors, nurses and diagnostic staff, and the extra investment needed to deliver it."
The first strike in January led to thousands of operations, procedures and appointments being cancelled across the NHS.
Wednesday's action is causing similar disruption, with analysis by NHS England showing 1,150 planned inpatient procedures have been cancelled alongside 1,734 day procedures.
Thousands more appointments are likely to be affected.
The major sticking point in the dispute is over weekend pay and whether Saturday should be largely classed as a normal working day.
Currently, 7pm to 7am Monday to Friday and the whole of Saturday and Sunday attract a premium rate of pay for junior doctors.
An offer from the Government in November said doctors would receive time-and-a-half for any hours worked Monday to Sunday between 10pm and 7am, and time-and-a-third for any hours worked between 7pm and 10pm on Saturdays and 7am and 10pm on Sundays.
In a further offer, ministers said that as part of an overall agreement, a premium rate of pay could kick in from 5pm on Saturdays rather than 7pm, and at 9pm Monday to Friday.
According to the Independent, an online poll of 1,045 medics found 922 were "prepared to consider resignation" should Mr Hunt follow through on his vow to impose the contract.
Meanwhile, a poll of 800 members of the public for the Health Service Journal (HSJ) has found that two-thirds of adults in England support the strike, although opposition appears to have grown slightly.
The author JK Rowling, who is married to a doctor, took to Twitter to say she is backing the strike.
She posted a graphic which read "I support the junior doctors #save the NHS". She added: "Speaking as a doctor's wife.."
Comedian and actor Sanjeev Bhakshar also showed his support on Twitter, saying: "#JuniorDoctorsStrike The alternative is an underpaid undertrained Dr who's been up for 20 hrs on caffeine treating my child in an emergency."
Controversial columnist Katie Hopkins expressed her opposition to the strike, saying on Twitter: "Junior doctor trying to explain why they need more cash to work a Saturday. 'It's very complex'. No love. It is simple. I diagnose greed."
Shadow health secretary Heidi Alexander, said: "Today's industrial action is deeply disappointing, particularly for the patients who have had hospital treatment delayed because of it.
"The sad truth is that it didn't have to come to this. Jeremy Hunt's handling of these negotiations has been a complete and utter shambles."