Lillard has sat out Portland's past five games due to a hamstring injury.
His return will correspond with a big debut for the Cavs, as they announced guard Isaiah Thomas will play Tuesday after he missed the team's first 36 contests with a hip ailment.
The 27-year-old Lillard is enjoying another strong year for the Blazers, as he is averaging 25.2 points, 6.4 assists and 5.0 rebounds per game.
Even so, Portland has survived without him, posting a 3-2 record during his recent absence.
Shabazz Napier started with Lillard out, but he'll move back to the bench and provide quality depth.
Portland is sixth in the Western Conference at 19-17, and it is 2.5 games clear of the ninth-place Los Angeles Clippers.
The Blazers will look to spoil Thomas' Cavaliers debut and extend Cleveland's losing streak to four games Tuesday.