Entering the game, San Francisco is slotted as the NFC's No. 6 seed. A win over the Colts at Lucas Oil Stadium would move the 49ers up to No. 5. From there, victories against the Chicago Bears and Seattle Seahawks would not only secure the NFC West title but also clinch the No. 1 seed in the NFC playoffs.
There is no shortage of motivation.
Indianapolis recently brought quarterback Philip Rivers out of retirement after starter Daniel Jones suffered a season-ending injury. But slowing the 44-year-old veteran is not the 49ers' top priority.
So what's the key to beating the Colts?
"Well, one thing about them is we've got to stop the run," head coach Kyle Shanahan recently told NBC Sports Bay Area's Matt Maiocco. "I mean, they're running the ball that well. I mean, it's very documented that they brought Philip Rivers in, and the best thing that a quarterback like that can have is a running game, and they've got a very good one, if not the best one."
Colts star running back Jonathan Taylor has rushed for 1,443 yards and 16 touchdowns this season, averaging 5.3 yards per carry. Containing him will be a major challenge.
"So we have to stop that and make them one-dimensional," Shanahan continued. "If we do that, I think we've got a good chance."
That task won't be easy. The 49ers' defense has struggled against the run at times, allowing more than 100 rushing yards in nine games this season, including each of the past two.
"There has been some good, some bad," defensive coordinator Robert Saleh said last week. "Didn't like the way we finished last week. I take responsibility for that fourth quarter. We're up three scores with nine minutes to go, playing more pass defense than run defense, and I think they got about 57 yards on that last drive and a little over 50 yards in the run game. But it's definitely got to be firmer."
Shanahan also expects a stiff test from the Colts' defense, especially with defensive tackle DeForest Buckner returning from injured reserve.
"I know they're getting Buck back, which will help them," Shanahan said. "They're probably the best team in the league in stopping the run, which—I know if we go out and just throw the ball against them, that's what they want you to do.
"You have to be able to run the ball versus a really tough run defense to balance it out so you don't turn the ball over. And if we can do that, then I know we'll be able to score points and not turn it over, and that'll give us the best chance to win."
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