The 49ers will have their lead running back, Raheem Mostert for this game as he returned last week against the Rams. While he is a threat and will see plenty of rushing attempts in this game, the one running back the Bills should be concerned most about is Jerick McKinnon.
The reason is that McKinnon is similar to Austin Ekeler in that he is an excellent pass-catching back out of the backfield. This past week, Ekeler caught 11 passes against the Bills for 85 receiving yards.
McKinnon doesn’t see a high volume of touches typically but has breakaway speed and knows how to find the end zone. He has six touchdowns, five rushing and one receiving, on 107 total touches this year.
It would not be surprising to see the 49ers use McKinnon in a similar role to what the Chargers did with Austin Ekeler and the Bills defense will need to do a better job limiting these type of plays.