The Wanderers sit second in their group with three games remaining but are only ahead of FC Seoul on goal difference, with the top two sides to go through to the knock out phase.
With Guanzhou Evergrande leading the group and Kashima Antlers last, Tuesday's clash at Parramatta Stadium will go a long way to deciding who clinches second.
Should the Wanderers win, victory against Kashima in a fortnight, also at home, would secure their progression.
Popovic has ruled out midfielder Nikita Rukavytsya, who injured his hamstring in the Wanderers' 1-1 draw with Melbourne City on Friday and joins the likes of Socceroos defender Matthew Spiranovic (hamstring), Brendan Hamill (thigh), Brendon Santalab (shoulder) and Shannon Cole (collarbone) in the casualty ward.
The coach rated Anthony Golec (groin) a possibility to play.
The Wanderers head into Tuesday's match on the back of late revival in the A-League after thumping Brisbane Roar 4-1 and holding City to a draw.
They will also take confidence from holding FC Seoul to a scoreless draw in Korea Republic last month, having eliminated it in the semi-finals last year.
The K-League side possess dangerous imports Mauricio Molina, Osmar Barba and Everton Santos, as well as a host of Korea Republic internationals, but Popovic said his side was not intimidated.
"Whoever we play in this competition, we're the champions so there's nothing to fear," he said.
"We know tomorrow [Tuesday] night they possess players who can win at any moment.
"But they also respect us. They know we beat them in the semi-finals last year and we took a point off them a few weeks ago.
But all that matters is we take the three points tomorrow.
"It's an important game that's for sure. I don't think it's do or die but you can take a step forward in our your chances of going through."
FC Seoul coach Choi Yong-soo feels it will all come down to Tuesday's match.
"It's a very hard group - we call it the group of death," he said on Monday.
"The game tomorrow game is a very big, important game. This game will be the decider."
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