Hughes, 17, who has started 17 of the Rams' 18 league matches this season, had to be replaced in injury time at the end of the 3-2 home win over Birmingham on Saturday evening after turning an ankle.
"We don't like making substitutions with 30 seconds to go but we did not want Will to make the ankle worse," said manager Nigel Clough. "I said to (Birmingham manager) Lee Clark that you could see Will was struggling. The substitution was not time-wasting, or anything like that."
Jeff Hendrick, rested against the Blues, is likely to replace his fellow academy product in the starting line-up should Hughes not make it.
Nathan Tyson is pushing for a recall after coming off the bench to score the winner against Birmingham but fellow forward Jamie Ward is likely to remain sidelined for an 11th match with his hamstring injury.
Cardiff manager Malky Mackay will be without suspended midfielder Simon Lappin.
The 29-year-old Norwich loanee became the first Cardiff player to see red since October 2010 when he was dismissed for picking up two yellow cards on his debut in Cardiff's 2-1 victory over Barnsley on Saturday.
Mackay is also likely to be without Ben Turner, Andrew Taylor and Kevin McNaughton who are recovering from hamstring, calf and thigh injuries respectively.
The trio missed their side's victory over Barnsley at the weekend and the trip to Pride Park looks to have come too soon for them as well.
The league leaders could hand a start to veteran striker Craig Bellamy, who made his ninth appearance of the season when he came off the bench at Oakwell.
Source: Cardiff City Online