Cain appeared to injure his left leg in the first series of the game and did not return to action.
"Love Noah, so much respect for Noah," Franklin said. "He really had an unbelievable offseason and worked really hard for this opportunity."
Cain, a sophomore, had suffered an ankle injury last season against Michigan State that caused him to miss much of the latter half of the season. He had 443 yards on 84 attempts and eight touchdowns last season in a limited capacity.
Cain had only three attempts for 13 yards this season in the first game and is now the second running back to miss the season, joining Journey Brown who is out with an undisclosed medical condition.
Brown led the team in rushing last season with 902 yards and 12 touchdowns, so with both Brown and Cain out, sophomore Devyn Ford will lead the ground attack for Penn State.
Ford was an ESPN 300 recruit along with Cain in the 2019 class, ranked as the No. 146 prospect overall.
Ford had 297 yards and three touchdowns last season as part of the running back rotation for Penn State.