The two sides met at Ewood Park just three weeks ago when a late David Lopez penalty cancelled out Jordan Rhodes' earlier strike from the spot as the points were shared in a 1-1 draw.
Rovers go into the match on the south coast high in confidence after three wins and three clean sheets since their last meeting, but Appleton knows it won't be easy against a Brighton side a place above them in the league.
"Tuesday night is going to be a difficult game," said the Rovers boss.
"It is going to be game where probably Brighton will have a lot more possession than us.
"We are going to have to be solid, structured and with the opportunities we get we are going to have to be clinical."
Tuesday's game continues a busy spell of matches for Rovers with the match against Brighton being the first of five further games between now and the end of the month.
I expect it to be slightly different," added Appleton. "It is what we do in between that is going to be really crucial over the next four weeks.
"We are going to have to really look after ourselves, the players are going to have to make sure that they look after themselves when they are away from the football club."