The Hammers will be without Skrtel's on-loan Reds team-mate Andy Carroll, who is out for two months with a knee injury, but Carlton Cole will provide a similar presence up front.
Cole's confidence was boosted when he netted his first goal of the season against Chelsea last weekend, but Skrtel believes he can keep the big forward quiet on Sunday.
"For me personally it is better if they play with a big striker because that is what I like," Skrtel. "I am more comfortable than playing against smaller guys.
"But it is no different who is playing, whether it was Andy or Carlton Cole. They are all dangerous and we have to focus and be careful for 90 minutes and don't let them score.
"I am looking forward to it and I'll try to do my best to make sure they don't. It is going to be a difficult game because it is going to be physical and we have to be ready for that.
"We have to play our game and try to beat them and I hope the quality is on our side and we can beat them.
"For me as a defender, but also for the whole team it is good when we don't concede a goal because that is where we start from.
"If you don't concede a goal you have a good chance of winning the game and I think we have tightened up in recent weeks."