The former Genoa coach has replaced Mauro Milanese - whose spell in charge came to an end on Monday after just 43 days - and has agreed a two-and-a-half year deal.
Ex-Italy and QPR defender Milanese, who took the job in October but won just two of his eight matches in the dug-out, has returned to his previous position as the club's sporting director.
Liverani, 38, told the club's official website: "I'm excited about this challenge and cannot wait to get started at Leyton Orient
This is a long-term project and we will work together to make it a success."
The former Italy international takes over a side hovering above the League One relegation zone on goal difference alone.
The O's have been a pale shadow of the side which led the table for much of last season, only to fall away towards the end and lose in the play-off final on penalties to Rotherham.
They were taken over by Italian businessman Francesco Becchetti in the summer and long-serving manager Russell Slade left in September to take over at Cardiff.
He was replaced by assistant Kevin Nugent, who lasted a month before Milanese was handed the reins.
But Milanese was unable to arrest Orient's slide and in his final match in charge they were dumped out of the Johnstone's Paint Trophy by Gillingham at the weekend.
Liverani's first match in charge will be at home to Peterborough on Saturday.
Source : PA
Source: PA