Firmino and Matip missed Liverpool's EFL Cup victory over Leeds but are expected to be fit in time for the Reds' trip to the south coast.
With Chelsea facing Manchester City, Liverpool could go top with a win if their fellow title challengers draw the game.
Firmino has been a key part of Liverpool's success this season, spearheading the Reds' attack alongside Sadio Mane and Philippe Coutinho, who will remain on the sidelines with injury.
Meanwhile, Matip has also impressed since moving to Anfield, with Liverpool yet to lose a game in which he has played.