The Slovakia defender may not have to face on-loan Anfield team-mate Andy Carroll, who would have been ineligible to play even if he had not been ruled out for two months with a knee injury, but expects a similar test from another big frontman, Carlton Cole.
Cole scored his first goal of the season in the 3-1 win over Chelsea last weekend and Skrtel knows he can be a handful - but that makes it even more enjoyable for the centre-back.
"For me personally it is better if they play with a big striker because that is what I like," Skrtel told Press Association Sport.
"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."
Defensive stability has returned to some degree in the last few weeks combined with players other than Luis Suarez finding the net.
As a centre-back, Skrtel takes great pride in the former as he admits Liverpool were shaky in defence earlier in the season as the team tried to adjust to new manager Brendan Rodgers' different ways of working.
"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," added the 27-year-old.
"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.
"Of course we know from the beginning of the season it wasn't working well because too many things had changed, but in the last few weeks we have started to play better and we are stronger at the back."
Liverpool have successfully bounced back from the ending of their eight-match unbeaten league run when even the performance in the defeat at Tottenham was encouraging.
Having beaten Southampton at home last weekend they progressed to the last 32 of the Europa League with a victory over Udinese in Italy.
Skrtel believes momentum is growing and insists they need to use that to mount a push for the top four, which is still tantalisingly in reach despite a disappointing start to the Reds' campaign.
The next month will probably determine - both on and off the pitch where January signings are expected to, at the very least, bolster the forward line - whether they in a position to mount a bid
"In the last three weeks we have got better and the confidence is growing," he added.
"It was a big game in Italy and we knew we had to win and we got it to get through to the next round.
"We just have to carry on this way and be better and better now.
"The period up to and over Christmas is very important and I think we have to get as many points as we can going from game to game and try to get closer to the top four."