City really need a win against Villa tonight to offset another disappointing away defeat - this time at West Ham - at the weekend.
But Hughes has lost Craig Bellamy to a knee injury that looks set to keep the Welshman out for a month and also the Brazilian Robinho, who has aggravated an ankle injury and will also not feature tonight.
With other strikers Benjani and Daniel Sturridge injured and the Bulgarian Valeri Bojinov feeling his way back from long-term injury, Hughes looks likely to turn to young Ecuadorian centre forward Felipe Caicedo tonight and hand troublesome Brazilian Elano another chance to impress.
Hughes said: 'Craig Bellamy and Robinho are not fit. Craig is having a scan on his knee where he has torn fibres and the best case scenario is two or three weeks. It could be about six weeks. It's disappointing because he has been outstanding since he came here.
'Robinho has got the same ankle injury he had when he came off against Arsenal but, hopefully, he'll only miss this match and be fit to play against Aalborg in the UEFA Cup.
'Sturridge still has got two weeks to go. Benjani only starts football training next week but his fitness is fine.
'So I've got two 20-year-olds Caicedo and Ched Evans to choose from - and Bojinov who's hardly ever played in the Premier League.'
West Ham United's Herita Ilunga, right, and Manchester City's Craig Bellamy vie for the ball
One of the manager's fears after City failed to meet the asking price for Blackburn's Roque Santa Cruz in January was that his attacking options would be light if any of his forwards suffered long-term injuries. This is what has happened.
Caicedo has scored goals for City this season but is dangerously inexperienced while the talented Elano has not played consistently under Hughes recently since the two fell out before Christmas.
'This situation is an opportunity for any player, whether he starts or comes on, to make an impact,' said Hughes. 'That is not just Bojinov and Elano, I would expect that of any player who gets that chance.
'It's a little bit early for Bojinov to start. He's had only two 45-minute practice games and 60 minutes in the reserves.
'You look at the Villa side this season and they've had the benefit of a settled side for most of the season and that is key.
'They've had a continuity of selection and steered clear of injuries which obviously has an impact on selection. We haven't had the benefit of that.'
Mark Hughes the Manchester City manager
O'Neill will be reliant on that continuity to deliver a higherplaced Premier League finish than he and the club had previously thought necessary.
The Irishman was unaware - until it was pointed out in Sportsmail yesterday - that if Arsenal were to win the Champions League they would automatically win the right to defend it.
That would mean, assuming Arsenal finished outside the qualification places, the fourthplaced team would miss out on Europe's premier club competition.
O'Neill said: 'As long as it was clear at the start of the season - then obviously I'll abide by it. But if they've just made it up in the past four or five days - which is very possible with Uefa - then that is a different matter.
'My view is this: if you have won the Champions League, then I think you should have the right to defend it next year. Arsenal are very capable of winning that competition. They are going to get their best players back in the next week or so. They are capable of winning it.
'However, we're still in there. It won't affect us. We shall be pushing for every point.'