Combinatorial　CpG　oligonucleotide　(CPG)　and　chemotherapy　drug　represent　a　promising　approach　to　reactivate　immune　system.　However,　these　two　agents　possess　different　physicochemical　properties,　hindering　the　application　of　direct　self-assembly　of　these　two　cargos　into　a　single　nanostructure.　Here,　a　multistage　cooperative　nanodrug　is　developed　by　the　direct　self-assembly　of　cis-platinum　(CDDP,　Pt),　l-arginine　(l-Arg,　R),　and　CPG　(defined　as　PtR/CPG)　for　antitumor　chemoimmunotherapy.　First,　the　CDDP　can　induce　cell　apoptosis.　Meanwhile,　CDDP　also　promotes　the　production　of　H2O2,　catalyzing　the　conversion　of　l-Arg　into　nitric　oxide　(NO).　The　generated　NO　decreases　the　multidrug　resistance　of　cells　toward　CDDP.　Thus,　the　synergistic　effects　of　CDDP　and　NO　can　trigger　immunogenic　cell　death　to　produce　tumor-associated　antigens　(TAAs).　The　TAAs　and　CPG　will　induce　the　maturation　of　dendritic　cells　(DCs)　and　enhance　antigen　presentation　ability　of　DCs.　In　this　way,　the　PtR/CPG　can　reverse　the　immunosuppressive　microenvironment,　sensitizing　tumors　to　immune　checkpoint　inhibitors　mediated　by　the　programmed　death-ligand　1　(PD-L1)　antibody.　Furthermore,　the　PtR/CPG　combined　with　the　PD-L1　antibody　decreases　the　exhaustion　and　dysfunction　of　cytotoxic　T　lymphocytes　to　elicit　durable　systemic　immune　response.　As　a　result,　the　prepared　PtR/CPG　nanodrug　in　combination　with　PD-L1　may　be　highly　significant　for　cancer　immunotherapy.　©　2021　Wiley-VCH　GmbH