Jefferies' men will close to within three points of their city rivals and one of Saturday's opponents with victory at Tynecastle.
Should Hibs then fail to beat title-chasing Rangers on Sunday, Hearts would arrive at Easter Road for the Edinburgh derby six days later with the chance to move level with John Hughes' faltering charges.
"This is a huge game for us now against Motherwell," said Jefferies, whose side lost 2-0 at Ibrox on Sunday.
"We always knew Rangers was going to be a difficult match for us but the most important thing was that Motherwell didn't pick up anything either at the weekend.
"If we can get the crowd behind us and get a win on Saturday, hopefully that will put pressure on Hibs. They play Rangers on Sunday and that is not going to be easy for them with what's at stake.
"If Rangers were then to win then there would be just three points between us and Hibs when we play them at Easter Road.
"That's why Motherwell is a key game for us and they will also be playing Hibs at Fir Park when we take on Dundee United at Tynecastle on Wednesday, May 5 - so it's very interesting.
"It's all to play for at the moment and with three games at home coming up, this is our best chance to give it everything."
Hearts are currently sixth in the SPL, with fifth place likely to guarantee Europa League football next season.
Jefferies had good news today on the fitness of Gary Glen and Laryea Kingston, both of whom have returned to training following hamstring injuries.
Jefferies told Hearts News Today: "We thought Larry might miss a couple of days but he trained yesterday and is fine so that's good news and Gary Glen will also be in contention this weekend, which is another positive."