The tie remains in the balance after last week's 1-0 outcome in Buenos Aires and the Brazilian side hope to turn it around against a side that have been watertight of late in the competition.
Match preview
Despite ending atop their group, Cruzeiro went into last week's last-16 first leg against Boca aware that it would not be a walk in the park, and so it proved.
Raposa were defeated 1-0 by their Argentine hosts, leaving them chasing the tie on home soil heading into this week's second leg.
Having failed to win on their turf by more than a single goal in the group stage — a 3-3 draw against Alianza, and 1-0 wins over Union La Calera and Universidad — the home support should expect a nail-biting second leg if that pattern persists against Boca.
It does not help that the Brazilian side are facing the two-time Sudamericana winners during their ongoing sequence of results, with Raposa winless in their last four matches in all competitions, losing two and drawing as many.
Having failed to win consecutive home matches in the Brasileiro — 2-1 defeat by Fortaleza and a goalless encounter with Atletico Mineiro — Fernando Seabra has reason to be nervous ahead of his side's bid to make the competition's quarter-final.
Those statistics will be music to Boca's ears heading into Wednesday night's encounter, as Diego Martinez's men hope to advance to the last eight after a positive outcome on home soil.
That marginal 1-0 win means Cruzeiro will believe a turnaround is possible, although the travelling support will back their team to keep another clean sheet in the competition's knockout stages.
Martinez's men needed one goal on home soil to settle the knockout round playoff tie with Independiente del Valle and they seek to do likewise after notching a 1-0 victory at their stomping ground last week.
They avoided defeat in two of their three away group-stage games, only losing 4-2 to Brazilian outfit Fortaleza either side of a goalless encounter with Nacional Potosi and a 2-1 win over Trinidense.
Having avoided losing since early June, the hard-to-beat Boca seek to continue their 11-match undefeated streak in all competitions in Belo Horizonte.
Cruzeiro Copa Sudamericana form:
D
D
W
W
W
L
Cruzeiro form (all competitions):
W
W
L
D
L
D
Boca Juniors Copa Sudamericana form:
W
D
W
D
W
W
Boca Juniors form (all competitions):
D
W
D
D
W
W
Team News
Cruzeiro could be without Rafa Silva due to a knee injury while Gabriel Veron (hamstring) is not anticipated to play any part for Seabra's men.
Juan Dinenno netted a brace for Cruzeiro in their recent 2-2 draw at Vitoria, possibly giving his manager something to ponder regarding his centre-forward options against Boca.
The away side will be without Chelsea-bound youngster Aaron Anselmino (ineligible) and Lille loanee Ignacio Miramon for the same reason, while Frank Fabra (strain) and Lucas Blondel (knee) are missing due to injury.
Legendary striker Edinson Cavani was the match-winner last week, and he should lead the attack for the Argentine side keen to add to his five Sudamericana goals.
Cruzeiro possible starting lineup:
Cassio; Ramiro, Ivaldo, Marcelo, Marlon; Romero, Walace, Barreal; Pereira; Jorge, Dinenno
Boca Juniors possible starting lineup:
Romero; Advincula, Medel, Lema, Blanco; Saralegui, Medina, Fernandez, Zenon; Merentiel, Cavani