The card will be the annual year-end event put on by the UFC, and takes place from the MGM Grand Garden Arena in Las Vegas.
"Cain is on a mission to get the belt back," UFC president Dana White said. "He wants to prove that he's still the best heavyweight in the world. But Junior is one of the hardest-hitting fighters ever and he proved that by knocking out Cain and Frank Mir in back-to-back fights. This is the perfect fight to end 2012."
Dos Santos did stop Mir, a former champion, earlier this year on the same card as the Velasquez-Silva bout. Velasquez won the belt from Brock Lesnar, and was making his first title defense when he ran into the Brazilian.
The winner of dos Santos-Velasquez will likely be paired up with former Strikeforce heavyweight champion Alistair Overeem in early 2013 - barring any serious injuries by the victor. Overeem will have his suspension lifted just a few days prior to the match in December.
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