The European and world champions currently sit top of Group I having won four and drawn two of their six matches thus far, but they are level with France on 14 points.
France, however, have played one game more than La Roja and, therefore, three points against Belarus would leave Vicente del Bosque's side needing just one point from their final clash with Georgia to secure automatic qualification.
Belarus, meanwhile, currently sit bottom of the group having taken just four points from their seven matches, but they could move above Georgia with all three points in Spain. The corresponding match in Belarus took place in October 2012, when Spain picked up all three points with a 4-0 win.
Swansea City's Michu could be in line for his international debut with Spain after replacing the injured David Villa in the squad last week. His inclusion was a surprise, however, with the likes of Roberto Soldado and Fernando Llorente both left out of the party.
Juanfran's club teammate Koke, who is primarily a central midfielder, has operated at right-back in recent matches and could also start, while Cesc Fabregas is expected to be deployed in the centre of the Spanish attack.
Meanwhile, Belarus have no fresh injury concerns from training this week and are expected to name their strongest available XI.
That means that Syarhey Vyeramko will continue in goal, while there will also be starts for the experienced Timofei Kalachev and Sergei Kornilenko, who has scored 13 goals in 58 games for his country.
Possible starting lineups
Spain: Casillas; Koke, Pique, Ramos, Juanfran; Xavi, Busquets, Iniesta; Pedro, Fabregas, Silva
Belarus: Vyeramko; Verkhovtsov, Martynovich, Filipenko, Bardachow; Kalachev, Kislyak, Tsiharow, Drahun; Kornilenko, Rodionov
Sports Mole says: 3-0