"We absolutely must win to have the chance of going further in the Cup," Forlan told reporters before the match against the African champions, who crushed tiny Tahiti 6-1 on Monday.
"They won the match they had to win, scored lots of goals and even a draw will be better for them than us," said the 34-year-old striker, best player at the 2010 World Cup.
"Nigeria have good players, many play in Europe, they are physically strong, it won't be at all easy, it will be a hard match," added Forlan, who will also be looking to add to his Uruguay tally of 33 goals.
Copa America holders Uruguay lost 2-1 to world champions Spain in their Group B opener on Sunday with Forlan coming on as a 69th-minute substitute.
A draw could leave Uruguay needing a big-scoring win in their last match against Tahiti and a Spanish win over Nigeria on Sunday to stand any chance of a place in the semi-finals.