Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death (ICD), which provides a promising alternative way for cancer immunotherapy. However, the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone. Herein, we proposed a trinity immune enhancing nanoparticles (TIENs) for boosting antitumor immune responses of chemo agents. The TIENs was constructed with Food and Drug Administration (FDA) approved polylactic acid (PLA), canonical proton-sponging cationic polymer polyethyleneimine (PEI), and Toll-like receptor 9 (TLR9) agonist cytosine phosphate guanine oligodeoxynucleotide (CpG-ODN). In in vitro studies, the TIENs was proved to (1) promote antigen capturing, (2) antigen-presenting cells (APCs) activation, and (3) antigen cross-presentation. In in vivo studies, intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models, respectively. Furthermore, after decoration with a detachable shielding, the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection. The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.