With four games left to play, the 23rd-placed Owls are seven points adrift of safety, while Rovers are 15th and have nothing to play for.
A defeat for Sheffield Wednesday, combined with a Derby County win over Preston North End, would see the Yorkshire outfit consigned to League One next season.
Wednesday's survival hopes were dealt a huge blow on Saturday as they conceded a late equaliser to draw 1-1 with Bristol City.
It is now three games without a victory for Wednesday, who have won just twice in their last 14 matches.
However, the strugglers are much stronger at home than they are away; they have lost just one of their last four matches at Hillsborough, while only the top three – Norwich City, Watford and Swansea City – have conceded fewer goals at home this season.
The home side will be keen to avoid a repeat of Blackburn's most recent visit to Hillsborough, as Rovers won 5-0 in South Yorkshire in 2019/20.
The success was a sign of Tony Mowbray's side's attacking potency that they carried into this season, but it is something that has faded in the second half of the campaign.
Only Preston North End (four) and Huddersfield Town (three) have won fewer Championship games in 2021 than Blackburn (five), but three of those have come away from home. Meanwhile, only Brentford, Norwich City and Bournemouth have scored more goals on the road this season than Mowbray's side.
Rovers currently sit 15th on 50 points and will be keen to end a disappointing campaign on a high as all of their final four games are against bottom-seven sides.
Smith said it was a "tough decision" to leave Jordan Rhodes out of the Sheffield Wednesday lineup against Bristol City, and the striker could return on Tuesday night.
Joost van Aken and Fisayo Dele-Bashiru both made their returns from injury as they were included in the matchday squad on Saturday, while Chey Dunkley is nearing a return at the end of a campaign clouded by injury.
Mowbray could name an unchanged team after hitting on a winning formula against Derby.
Midfielder Lewis Travis completed 90 minutes for the first time since the beginning of February against the Rams and has called on his teammates to "win all of the remaining games" to secure a top-half finish.
Elliott's winning strike on Friday was the teenager's first goal in 11 appearances, and he will be keen to end his loan spell at Rovers in good form as his stock continues to rise.
Sheffield Wednesday possible starting lineup:
Westwood; Hutchinson, Lees, Borner; Palmer, Pelupessy, Bannan, Reach; Windass, Harris; Rhodes
Blackburn Rovers possible starting lineup:
Kaminski; Nyambe, Harwood-Bellis, Branthwaite, Douglas; Travis, Johnson, Holtby; Elliott, Armstrong, Gallagher
We say: Sheffield Wednesday 1-0 Blackburn Rovers
In truth, nothing less than a win will be good enough for Wednesday if they are to stay in the Championship. We think that they will get just that though against a Blackburn side that will have taken confidence from their win over Derby but are too inconsistent to convince of consecutive victories.
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