Platinum complexes, despite being the most successful organometallic anticancer chemotherapy drugs, still suffer from serious side effects and therapy resistance. Inspired by the immunomodulation effect of platinum drugs, an epigenetic platinum(IV) complex was synthesized for enhanced cancer chemoimmunotherapy by conjugating oxidized oxaliplatin (OXA) with 2-bromo-1-(3,3-dinitro-1-azetidinyl)ethenone (RRx-001), the latter of which as a nitric oxide (NO) donor is also an epigenetic agent. The obtained complex (named OXA-NO) could significantly increase the level of "eat me" signal CRT expression and decrease the level of "don't eat me" signal CD47 expression on cancer cell membranes to promote their phagocytosis by macrophages. In addition, OXA-NO could release nitric oxide to trigger the transformation of pro-tumorigenic M2-type macrophages into antitumor M1-type macrophages within the tumor to reverse the immunosuppressive tumor microenvironment. Compared to commercial OXA, OXA-NO exhibited much stronger tumor growth inhibition ability and was much better tolerated, with obviously weakened side effects observed in spleen, lung, and kidneys. Therefore, this epigenetic platinum(IV) complex that exhibits excellent therapeutic efficacy and safety has great potential in the clinic.