Although the Potters have a decent recent record in the competition, the Stoke boss admits it will be a difficult task winning in south London.
The teams meet on January 5 and Pulis told the club's website: "Once you step outside of the Premier League, it doesn't get any more difficult than drawing one of the top teams in the Championship away.
"I am sure they will be up for it, and their fans too, and we have to go there and be ready for whatever is thrown at us.
"The Premier League will always be the most important thing for us, of course, but we've also shown in recent years how seriously we have taken and respected the FA Cup.
"In the last three years we've reached a final (losing to Manchester City) and been beaten in the quarter-finals at Chelsea and Liverpool.
"We'd love another crack at such a great competition again but the draw has obviously made it an extremely difficult first hurdle to get over."