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7 year oldMr Mnuchin is outlining his experience and qualifications to hold one of the most important jobs in finance.
In an opening statement, he rejected claims his OneWest Bank was a "foreclosure machine" that ruined lives during the housing crash.
"I have been maligned", the ex-hedge fund boss told the Finance Committee.
Mr Mnuchin, who spent 17 years at Goldman Sachs before leaving in 2002 to set up an investment group and fund Hollywood movies, is facing some tough questioning during the hearing.
That he has been forced to to defend his record during his opening remarks underlines the hostility some people feel towards his appointment.
Elizabeth Warren, an anti-Wall Street Democratic senator, has already set up a forum where former OneWest foreclosure victims could air their complaints.
But Mr Mnuchin, whose fiancée and children are also at the hearing, told the committee: "Since I was first nominated to serve as treasury secretary, I have been maligned as taking advantage of others' hardships in order to earn a buck. Nothing could be further from the truth."
He said he felt "enormous sympathy" for people who last their homes "because the system failed them".
However, Senator Ron Wyden, the Finance Committee's top Democrat, criticised Mr Mnuchin's OneWest for its automated "robo-signing" of foreclosure documents.
He also criticised Mr Mnuchin's use of tax havens such as Anguilla and the Cayman Islands to shelter hedge fund profits, questioning his qualifications to oversee a major revamp of tax laws to make them fairer to working Americans.
"In Mr. Mnuchin's case, millions of dollars in profits from Hollywood exports like the movie 'Avatar' were funnelled to an offshore web of entities and investors," Mr Wyden said in his opening remarks.
The US treasury secretary is the leading government voice on domestic and international economic policy and one of the key figures shaping US financial strategy.
So, Mr Mnuchin will face questions on how he will manage Mr Trump's tax and spending plans, which could significantly increase the US deficit, fuel inflation and further boost the dollar's value.
In one of the early exchanges, Mr Mnuchin said that the Trump administration would follow trade policies to ensure a strong US dollar.
"I will enforce trade policies that keep our currency strong on the global exchanges and create and protect American jobs," he said.
During questioning Mr Mnuchin said:
Last year, when he was put forward by Mr Trump, Mr Mnuchin vowed to introduce "the most significant middle income tax cut since [Ronald] Reagan".
Mr Mnuchin told CNBC: "We think by cutting corporate taxes we'll create huge economic growth and we'll have huge personal income... Taxes are way too complicated and people spend way too much time worrying about ways to get them lower."
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