Meanwhile, the visitors are looking to go three league matches unbeaten and move out of the relegation zone, where they have been since early November.
Sassuolo's seven-game unbeaten run away from home came to a notable end as they were thrashed 5-1 away at Atalanta last weekend.
La Neroverdi missed the chance to move into third place in Serie A with defeat seeing them slip to sixth, four points behind Roma in fourth place.
Forward Francesco Caputo, who has six goals in 10 league appearances this campaign, returned to the side after a spell on the sidelines with an injury but failed to make an impact in what was a bad day at the office for Roberto De Zerbi's side.
Nevertheless, Sassuolo will be pleased with their start to the 2020-21 campaign and have belief that they can improve on last season's eighth-placed finish and qualify for one of the European competitions.
Sassuolo cruised to a 5-0 victory against Genoa in their previous meeting last season and will hope to replicate that performance and result on Wednesday afternoon.
Victory in midweek would be their eighth in the league this campaign and could see De Zerbi's men move up to fifth if Napoli fail to beat Spezia.
Il Grifone had endured a 12-match winless streak under former boss Rolando Maran, who as a result was sacked and replaced by Ballardini, who has returned for a fourth spell in charge of the Liguria-based outfit.
The 56-year-old has the task of guiding Genoa out of the drop zone for the second time in his career, after successfully avoiding relegation in the 2012-13 campaign.
Genoa could move out of the relegation zone and climb as high as 15th if they were to secure their second successive away victory on Wednesday.
Sassuolo Serie A form: DWDLWL
Genoa Serie A form: DLDLWD
Sassuolo possible starting lineup:
Consigli; Toljan, Chiriches, Ferrari, Kyriakopoulos; Locatelli, Lopez; Berardi, Traore, Boga; Caputo
Genoa possible starting lineup:
Perin; Masiello, Zapata, Criscito; Zappacosta, Behrami, Badelj, Rovella, Czyborra; Pjaca, Destro
We say: Sassuolo 3-1 Genoa
Despite Genoa's mini revival in recent weeks, Sassuolo – who have scored 10 goals in their last two home matches against them – have looked stronger throughout this season and should have enough to secure the three points.