Tsitsipas eases into 'serious business' Lyon last four against Musetti
Greece's Tsitsipas eased past Japan's Yoshihito Nishioka 6-3, 6-4 in 66 minutes for a career best 31st win of the season.
The two-time Grand Slam semi-finalist is favourite for the Lyon title on clay just nines days from the start of the French Open.
"It was a good match from my side, he was serving well," 22-year-old Tsitsipas said.
"His game is a little unpredictable and he is one of the best left-handers out there. I knew he was going to fight and not give up.
"Tomorrow is going to be serious business and I know he (Musetti) can play well on this surface and elevate his game," he added.
Italian 19-year-old Musetti overcame world number 55 Aljaz Bedene 6-3, 7-6 (7/2) to claim his last four spot.
"He (Tsitsipas) is one of the best guys on Tour," Musetti said on Friday.
"I will try to lead the match and try not have him dominate me,” he added.
Elsewhere, Russian Karen Khachanov 6-1 7-6 (7/3) beat 34-year-old Richard Gasquet to celebrate his 25th birthday by reaching his first semi-final on clay.
Khachanov, ranked 26th in the word, will play either French qualifier Arthur Rinderknech or Briton Cameron Norrie.
Their quarter-final was postponed to Saturday due to rain with Norrie leading 1-0 in the third set after winning the first 6-3 before losing the second by the same score.