Platinum-based chemotherapeutic drugs as a component of combination chemotherapy are widely used in the treatment of cancer. In particular, oxaliplatin(L-OHP), one such platinum-based chemotherapeutic drug, has a synergistic effect in combination with 5-FU and Leucovorin for the treatment of advanced colorectal cancer. However, the underlying molecular mechanism of this synergistic effect has not been fully clarified yet. In this review, we summarize several updates about the in vitro action of oxaliplatin in human tumor cells and discuss the underlying mechanism of its synergistic effect with 5-FU.