The Syli National are on three points from two matches and need to beat the Black Stars to boost their chances of a place in the last eight on six points.
Even defeat could still see them progress, depending on the result of the tie between Mali and Bostwana being played at the same time in Libreville.
Four-time winners Ghana defeated Guinea 2-1 the last time both teams clashed in the Nations Cup in 2008.
Guinea go into this game on a high after trouncing Botswana 6-1 on Saturday following the narrow 1-0 loss to Mali in the opening fixture.
Only Egypt in 1963 and the Ivory Coast in 1970 have scored as many goals in the Nations Cup tournament proper as Guinea recorded at the weekend.
“We made a big statement. And now we will do everything to stay on in Gabon. We are determined and we have to play at a very high level,” said Guinea coach Michel Dussuyer, whose team upstaged star-studded Nigeria to reach this tournament.
“We know that against Ghana we will have to do more.
“I respect Ghana, they are a high level team with some great players. They did well at the 2010 World Cup and also reached the final of the last Nations Cup.
“They are a top team, but we want to win and qualify for the quarter-final. We don’t wish to go back home yet.”
“This tournament is very open, some of the favourites have already left, while Gabon and Equatorial Guinea are through to the quarter-finals,” he added.
Bastia striker Sadio Diallo crowned his first start of the Nations Cup with two well-taken goals against Botswana.
And he also vowed that this was a win-or-bust game for the Syli National.
“We will continue to work hard. We will play hard and not joke against Ghana,” said the 21-year-old striker.
Diallo as well as youngsters Abdoul Razzagui Camara and Ibrahima Traore have caught the eye in Gabon with some game-winning performances playing alongside experienced campaigners like Bobo Balde, Pascal Feindouno and skipper Kamil Zayatte.
For their own part, Ghana laboured to beat debutants Botswana before they turned on the class in the second half to beat Mali 2-0.
If the 2010 World Cup quarter-finalists win their group, they will face either inspired co-hosts Gabon or Tunisia in the next round.
However, they have insisted that they are not particular about staying clear of any team as they aim to end a 30-year trophy drought.
“We have quality players and we don’t care who we meet when we qualify for the quarter-finals. We are prepared for any team and we will take our chances, said ‘Baby Jet’ Asamoah Gyan, who scored a goal and created another as Ghana dumped Mali.
“What is most important is that we should be ready for whoever comes by because we want to qualify for the semi-finals,” added Ayew, who scored the second goal to cap another hard-working performance against Mali.
Skipper John Mensah should be fit after a muscle injury, he has served a one-match suspension for his red card against Botswana.
His return will give coach Goran Stevanovic a pleasant selection headache as he could pick any of his four central defenders following also the availability of Hoffenheim ace Isaac Vorsah after a two-match suspension.
The less established John Boye and Jonathan Mensah have covered for the Black Stars in the absence of top stars John Mensah and Vorsah.