To explore whether PH-sensitive doxorubicin/CTLA-4 siRNA nanocarriers can activate anti-tumor immunity and inhibit the growth of renal clear cell carcinoma. Methods PH-sensitive doxorubicin /CTLA-4 siRNA nanocarriers (P-LDs) were chemically synthesized. The morphology of P-LDs was observed by electron microscopy, and the particle size was determined by differential scanning calorimetry. The uptake of P-LDs by splenic lymphocytes was monitored by flow cytometry. The expression of CTLA-4 in splenic lymphocytes was detected by Western blot. In vivo distribution of P-LDs and tumor size were observed by IVIS. The expression of CTLA-4, IFN-γ and Ki67 in tumor tissues were detected by immunohistochemistry. Results P-LDs was uniformly spherical with a particle size of about 60 nm. P-LDs could effectively mediate siRNA transfection of splenic lymphocytes (P＜0.0001) and reduce the expression of CTLA-4 (P＜0.001) under low PH conditions. P-LDs could also effectively mediate siRNA transfection into tumor cells (P＜0.01) and inhibit tumor growth in vivo. After P-LDs treatment. The expression of CTLA-4 was significantly decreased (P＜0.0001), the content of IFN-γ was significantly increased (P＜0.0001), and the content of proliferation marker Ki67 was significantly decreased (P＜0.001).Conclusion P-LDs, a PH-sensitive nanocellular carrier, can effectively enrich adriamycin and si-CTLA-4 in tumor tissue, thereby inducing tumor cell apoptosis, enhancing local anti-tumor immune response and inhibiting tumor growth.