Last season, the Guinean champions’ campaign ended at the quarter-final stage, which is so far their best outing in this competition.
Now they are looking to surpass that and reach the semi-finals.
But their attempt faces a stern test against two-time champions Wydad Casablanca, whose last triumphant exploits in this tournament was as recent as 2017.
Horoya go into this battle without the suspended duo of defensive midfielder Djibo Wonkoye and Ghanaian central defender Godfred Asante.
The absence of the two players might not worry coach Didier Gomes, who is facing a Wydad side that appears to have little threat in attack.
The Moroccans’ strikers have failed to come to the party with goals this season, leaving defender Mohammed Nahiri as their top scorer with three goals.
Wydad boast of one of the best brains in African football in Tunisian coach Faouzi Benzarti, who led the Carthage Eagles to this year’s African Cup of Nations (Afcon) before being fired with one game to go.
While Horoya are eyeing a maiden semi-final spot, Algerian champions Club Sportif Constantine are also eager to write the same piece of history when they host defending champions Esperance at the Stade Mohamed-Hamlaoui.
Constantine have already broken barriers by reaching the group stages for the first time this season and now look to further their Champions League run.
With ex-Cameroon coach Denis Lavagne leading their technical bench, Constantine have enough guidance to help them reach the last four.
But battle-hardened Esperance stand in their way, wounded from last weekend’s Caf Super Cup defeat to Raja Casablanca.
Elsewhere, five-time champions Tout Puissant Mazembe have received a timely boost after veteran forward Tresor Mputu recovered from malaria ahead of their confrontation with Simba Sports Club in Dar es Salaam.
The Congolese giants are in territory where Simba appear incinvible, having beaten Al Ahly and AS Vita this season.
Mputu is aware of how Simba have turned the Benjamin Mkapa Nationbal Stadium into a fortress, where they have won all their Caf Champions League matches this season.
“All the teams have fallen in front of Simba SC on this field, but we are competitors and we know what to do. There are quality players in the team, experienced players and young people who have taken in the taste of competition.”
However, while Mputu is fit to play, another striker Ben Malango could not recover from injury.
But Mazembe’s coach Pamphile Mihayo might not worry much as he still have what appears to be a lethal strikeforce that has have Kevin Mondeko, Jackson Muleka and Mputu at his disposal.
Just like Mazembe, also treading in a potential minefield are Al Ahly, who visit Mamelodi Sundowns in Pretoria.
Al Ahly boast eight Champions League titles and are out to avenge the agony of finishing as runners-up in the last two seasons.
But they are coming up against a Sundowns side that has been consistent in Africa in recent seasons, including winning the 2016 edition.
While Sundowns have established themselves as a solid side that can upset any team on the continent, their coach Pitso Mosimane has chosen to be diplomatic, showering praise on Al Ahly.
“It's (Al Ahly) a big club, a very big club. It's bigger than Wydad if you thought Wydad is big. it's bigger than Esperance. It's huge, team of the century,” Mosimane was quoted as saying by Kingfut.
“They are the biggest team on the continent. Just look at the badge, just look at the stars. Then you realise that we are small boys, we have not done anything.
“They make transfers of $6 million; can you believe that in Africa? We sell players for less than that to Europe. They got Ramadan Sobhi from the English Premier League (Huddersfield), they brought him back. I mean how much do they need to pay?”
Sundowns will be missing injured Liberian forward Antony Laffor but with this season’s Champions League top goal-scorer Themba Zwane available, Mosimane can afford not to worry.