"I believe, as the unions do, that we need a strong rail service, a strong SNCF, and I respect their struggle," Macron told TF1 television in his first comments on the rolling strikes launched last week.
"But I'm also asking them to fully consider the needs of our fellow citizens who have to put up with this, of the companies that could fail because of this strike," Macron said.
"The right answer is not to abandon this reform, but to carry it out together," he said.
"But I am going to see this through to the end."
Unions are orchestrating stoppages for every two days out of five until at least June 28, causing extensive cancellations and disruption for the 4.5 million daily passengers on the network.
They oppose both the transformation of the SNCF into a joint-stock company whose shares would be held by the state, and a decision to deny job-for-life and early retirement guarantees for new hires.
Shortly after Macron's interview, the SNCF announced that one in three high-speed TGV and regional trains would be running on Friday as the next wave of two-day stoppages gets under way.
That would be less severe than on previous strike days, when just one in five or even one in eight TGVs were operating.
Macron, who again told of his own grandfather's job as a rail worker, said he understood the often difficult hours and constraints for SNCF employees.
But he said the company needed more flexibility for organising its operations ahead of the looming opening of the European passenger rail market to competition starting in 2020.
"This SNCF can't work if I tell 25-year-olds today that 'You'll be hired under the same terms as my grandfather' -- because that's basically what we're telling them. It's not workable," Macron said.
"In Germany they made more or less the same reform. And look at what happened: better service, more people taking the train, and more regional lines," he said, accusing unions of trying to scare people by saying some loss-making regional lines could be closed.
Macron said the state would gradually take on some of the nearly 47 billion euros of debt accrued from the development of the SNCF's infrastructure "bit by bit, as the reforms proceed".
He said that passengers had already done their part by accepting higher ticket prices, and that the state would invest "10 million euros per day for ten years" in network upgrades.
"This reform requires an effort by everyone," Macron said.