Both fly-half Russell and full-back Hogg are missing as a result of injuries suffered late on during last week's 22-7 defeat by Grand Slam-chasing Ireland in Edinburgh.
Blair Kinghorn, who had several consecutive starts in the Scotland number 10 shirt last year, will replace Russell and Ollie Smith will come in for Hogg, as happened during one of the 2022 Tests away to Argentina.
Both Russell and Hogg are hugely influential figures in Scotland's attack.
Russell was a central figure in their opening wins over England and Wales this Six Nations, while Hogg picked up his 100th cap against Ireland.
"We had a similar situation in the summer, when players stepped up in attacking roles, but also stepped up in general play and in terms of our defence," said Townsend when asked if his reshaped back division could cope.
He added: "So, we've that experience when going up against a top team (without Russell and Hogg), and that's what we're going up against this week in Italy."
Kinghorn's club position
There had been speculation that 26-year-old Kinghorn, a replacement full-back in recent matches, would start at number 15 against Italy.
But Townsend has opted to deploy him at stand-off instead, with Smith at full-back.
"We see Blair as a 10 who can play a number of positions," said Townsend as he explained his thinking in fielding the Edinburgh man at fly-half.
"It's his club position, I know he's had to play in the back three because of injury at Edinburgh but he's played there (fly-half) for the last two seasons.
"He played there for us in last year's Six Nations, three Tests in the summer and was involved in two Tests in the autumn, one he started and one he came off the bench. He's trained a lot at 10."
Up front, Townsend has had to make another change to his XV, with Edinburgh lock Sam Skinner replacing Richie Gray, who suffered rib damage against Ireland.
Townsend has brought in Edinburgh flanker Hamish Watson at the expense of Matt Fagerson, now among the replacements, in the only unforced alteration to the run-on side.
Uncapped Munster fly-half Ben Healy could make his Scotland debut off the bench.
Victory on Saturday would likely seal third place in the Six Nations for Scotland after their opening wins were followed by losses to France and Ireland.
Italy have lost all four of their Six Nations matches so far this season but Townsend insisted the Azzurri could still cause Scotland problems.
"They have beaten Australia in November, they beat Wales away last year," he said. "They are growing and the way they play puts teams under pressure because they attack from everywhere."
Scotland (15-1)
Ollie Smith; Kyle Steyn, Huw Jones, Sione Tuipulotu, Duhan van der Merwe; Blair Kinghorn, Ben White; Jack Dempsey, Hamish Watson, Jamie Ritchie (capt); Jonny Gray, Sam Skinner; Zander Fagerson, George Turner, Pierre Schoeman
Replacements: Ewan Ashman, Rory Sutherland, WP Nel, Scott Cummings, Matt Fagerson, Ali Price, Ben Healy, Cameron Redpath
Coach: Gregor Townsend (SCO)
