Boris Johnson warned train passengers they must “stay the course” in the face of the “unnecessary aggravation” caused by rail strikes.
The Prime Minister told a meeting of the Cabinet that reforms are vital for the rail industry and those who work in it.
Millions of people are suffering disruption as only a fifth of trains are running on Tuesday and half of lines are closed.
Services are generally restricted to main lines, but even those are only open between 7.30am and 6.30pm.
Around 40,000 members of the Rail, Maritime and Transport (RMT) union at Network Rail and 13 train operators have walked out in a bitter dispute over pay, jobs and conditions.
Mr Johnson said: “I say this to the country as a whole, we need to get ready to stay the course.
“To stay the course, because these reforms, these improvements in the way we run our railways are in the interests of the travelling public, they will help to cut costs for farepayers up and down the country.”
But the modernisation programme is also in the interests of workers because “if we don’t do this, these great companies, this great industry, will face further financial pressure, it will go bust and the result will be they have to hike up the cost of tickets still further”, he warned.
That would result in the “disaster” of declining rail use.
Usually busy stations such as London Euston are nearly deserted except for union picket lines.