Here's a look at three things to watch from the 49ers perspective in this one:
Making the most of Mariota's mistakes
The Titans got good news when it was revealed that quarterback Marcus Mariota is dealing with nothing more than a sprained knee, as opposed to something more serious. But that doesn't necessarily fix Tennessee's issues with Mariota's recent performances.
In three of Tennessee's past four games, Mariota has thrown multiple interceptions and his eight picks since Week 11 are three more than anyone else in the NFL. For the season, Mariota has thrown 14 interceptions with all of those miscues coming when he's not under pressure, according to ESPN Stats & Information.
Mariota's struggles on the road have also coincided with the Titans' inability to consistently play well away from home. Tennessee is 3-4 on the road this season and Mariota has just three touchdowns with 11 interceptions in those games. Mariota's road passer rating is just 60.5.
While Mariota looks like he'll be able to play against the Niners, he's unlikely to be at full strength, which means the Niners should be able to get after him without having as many concerns about his ability to run. On the bright side for Tennessee, it appears left tackle Taylor Lewan will be ready to go for an offensive line that has been among the best in the league in pass protection this season. They'll need him to be on point to help keep Mariota clean.
What's more, if recent trends hold, Mariota will give the 49ers defense some opportunities to get takeaways and turn the game. That unit must take advantage of those opportunities if the Niners are to walk away with their first three-game winning streak since 2014.
Pass protection priority
49ers quarterback Jimmy Garoppolo has started twice and faced very different pass rushes in each game. Against Chicago, Garoppolo was barely touched, allowing him to sit in the pocket and deliver passes at all levels of the defense. Against Houston, Garoppolo was under fire for most of the day and took his share of hits, though he made it through without any real scares.
Based on what the Titans have done lately and the fact that right tackle Trent Brown is out with a shoulder injury again, leaving veteran Zane Beadles to start at right tackle, it's a safe bet that Garoppolo will face pressure far more similar to what Houston provided than to what Chicago did.
In two of their past three games, the Titans have put up eight sacks, and they have a whopping 20 sacks in those three contests, the most in the NFL in that span. The key to that success? Tennessee has brought the blitz far more frequently, sending at least one extra rusher on 40 percent of opponent drop backs compared to 30 percent through the first 10 games of the season.
That figures to be a big challenge for a San Francisco offensive line that is tied for 24th in the league in pass protection rate, controlling the line of scrimmage on just 47 percent of drop backs.
Tennessee's defense can be beaten with the pass, giving up 233.3 passing yards per game (22nd in the NFL) though it doesn't give up many big plays through the air. For the Niners to have any success there, though, they'll need to ensure Garoppolo is upright for most of the game.
Garoppolo's toughest test yet
Speaking of Garoppolo, it's safe to say this will be the biggest test of his three starts and give us an idea of just how far along he is in learning and executing coach Kyle Shanahan's offense. The Titans defense is stout and has carried the freight in keeping Tennessee in the postseason mix.
As it stands, Garoppolo is 4-0 in his first quartet of NFL starts and with a win Sunday, he'd be the fifth quarterback in the past 20 seasons to win each of his first five starts and the first to do it since Pittsburgh's Ben Roethlisberger in 2004.
So what can Garoppolo do for an encore to his encore after throwing for 334 yards in his second start? Well, he could continue to make franchise history, for one. Garoppolo's 627 passing yards in his first two starts are the most by a Niner in franchise history. He needs just 141 yards to set the record for the most in a San Francisco quarterback's first three starts.
This week also is the start of a stretch in which Garoppolo and the Niners will face three of the top 11 teams in defensive efficiency. Tennessee currently sits fourth in that category.
It's asking a lot of Garoppolo to expect him to go out and put up big numbers again this week, and reality says he's probably going to hit some bumps along the way sooner or later. So far, though, he's proved pretty unflappable, and if he can do enough just to get the Niners another win, none of the other statistics will matter much.