The AFC's current No. 3 seed, the Tennessee Titans, will host the NFC's No. 6 seed, the San Francisco 49ers, in a Thursday Night Football showdown set for Week 16.

The Niners have won five of their last six games, while the Titans – who began the season as one of the hottest teams in the league — have dropped three of their last four matchups.

Injuries continue to ravage Tennessee, who will be without veteran wideout Julio Jones and two-time Pro Bowl running back Derrick Henry. They also lost wide receiver A.J. Brown to a chest injury in Week 11.

The 49ers will also be without lead running back Elijah Mitchell, but got a huge performance from backup Jeff Wilson Jr. (110 yards on 21 carries) in Sunday's 31-13 victory over Atlanta.

The Niners will enter Thursday's matchup as a three-point road favorite.

Let's see how the public is betting the moneyline, point spread, totals and more at TwinSpires Sports ahead of Thursday's matchup between the 49ers and Titans.

With the way the Titans are trending, bettors are favoring the road team in this matchup.

Nearly 60% of tickets and 70% of handle is backing the Niners to win outright.

San Francisco owns a 9-5 record in the head-to-head series, and won the most recent outing, 25-23, in 2017.

In Tennessee's three other games against NFC West opponents in 2021, the team has gone 2-1, with victories against the Los Angeles Rams and Seattle Seahawks.

Bettors also favor the Niners to cover the three-point spread, with 66% of tickets and 84% of handle placed on San Francisco -3.

The 49ers are 5-1 ATS in their last six games overall, and 4-1 ATS in their last five games as a favorite.

The Titans are 5-2 ATS in their last seven games as an underdog, but 1-4 ATS in their last five games overall.

Though both of these teams rank in the top 10 in points allowed, totals bettors like the Over (44) on Thursday night.

The Over has hit in three of Tennessee's four games following a straight-up loss, while the Over is 4-1 in the 49ers' last five Thursday games.

The Over is also 4-0 in the last four meetings between these teams and has hit in 10 of the Titans' last 14 games as an underdog.

For those leaning toward a lower-scoring game, the Under is 4-1 in the 49ers' last five games versus a team with a winning record, and it's 5-2 in Tennessee's seven home games this season.

Most popular prop bet: Deebo Samuel to score an anytime touchdown

As for prop bets, the most popular wager ahead of Thursday's contest is Deebo Samuel to score an anytime touchdown.

The Niners' top receiver (1,088 yards) has not only scored five receiving touchdowns, but he leads his team in rushing scores, with seven.

Samuel has run for at least one touchdown in his last five games, and recorded two rushing scores against the Minnesota Vikings.

Tennessee gives up an average of 2.4 touchdowns per contest, and Samuel is a solid bet to reach paydirt, either with a touchdown reception or on the run.