The MYC and RAS oncogenes were found early on to cooperate in the transformation of nonimmortalized primary cells, and in tumor development in transgenic mouse models. MYC prevents RAS-induced senescence. Moreover, tumor regression resulting from the suppression of MYC expression is associated with cellular senescence. How MYC prevents RAS-induced senescence and why suppression of MYC in tumors causes senescence remains to be elucidated. Here, we show that MYC interacts with the Pol β DNA polymerase and stimulates its enzymatic activities to accelerate the repair of oxidative DNA damage by the base excision repair (BER) pathway, thereby enabling RAS-driven cancer cells to avoid senescence and continue to proliferate despite producing excess levels of reactive oxygen species. The carboxy-terminal domain of MYC, which is needed for heterodimerization with its MAX partner and DNA binding, is not required for the DNA repair activity of MYC. Ectopic expression of MYCΔCTD accelerates DNA repair, protects against RAS-induced senescence, and cooperates with RAS in the transformation of primary cells, whereas MYC mutants inactive in DNA repair exhibit weaker or no activity in these assays. These results demonstrate that the function of MYC in BER plays an important role in the MYC-RAS cooperation.