The Samoan international winger, back from World Cup duty, replaces Andy Forsyth in the Tigers backline, while Sam Harrison also makes his first Premiership start of the season at scrum-half.
In the forwards, Julian White returns at tighthead prop after missing the last two games and Geoff Parling continues in the second row after making his comeback from injury last weekend.
"It's great to see Alesana Tuilagi and Martin Castrogiovanni back at the club this week," said Tigers director of rugby Richard Cockerill.
"Castro has returned with a slight hamstring injury but with Julian White back to fitness we want to give him time to recover fully. Alesana enjoyed probably his best-ever season with us last year so it's great to have him back and in the team.
"It is important for us to have those world-class players back in the squad and it is important for the supporters too.
"We've had a tough start to the season and Quins have been going very well, but we'll battle on and we'll certainly be up for it on home soil at Welford Road."
Harlequins have made just one change to the starting line-up that defeated Sale last Saturday at the Stoop.
The team sees Joe Marler coming into the front row to join up with Tim Fairbrother and Chris Brooker.
The bench sees the return of Joe Gray, having missed last week, and Mark Lambert takes his seat in place of Marler.
The 23-man squad continues to show home grown English talent at its spine with 21 English qualified players and 10 of the starting line up having graduated from the Quins academy system.
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