BACKGROUND This study investigated the correlation of programmed death 1 (PD-1) and T cell immunoglobulin and ITIM domain (TIGIT) with clinicopathological characteristics of renal cell carcinoma (RCC) and explored the biological roles of both proteins in the development, metastasis, and invasion of RCC. MATERIAL AND METHODS The expressions of PD-1 and TIGIT were detected in the RCC and adjacent normal tissues, and their correlation with the clinicopathological characteristics of RCC, relationship between PD-1 and TIGIT in RCC, and the correlation of PD-1 and TIGIT expression with distance of adjacent normal tissues to RCC were further evaluated. RESULTS TIGIT and PD-1 expression was detectable in the immune cells of peripheral blood mononuclear cells and lymphoid tumor infiltrating lymphocytes, and TIGIT expression was significantly higher than PD-1 expression in the same sample. Cells with transparent cytoplasm were diffuse, and several cells showed dark nuclear staining with mild atypia; the interstitium was rich in blood vessels and had mild fibrous hyperplasia, and immunofluorescence staining showed cells were positive for TIGIT. The expression of PD-1 and TIGIT was significantly different between RCC and adjacent normal tissues (P<0.05). Positive PD-1 expression was closely related to tumor size and Fuhrman grade (P<0.05). The expression of TIGIT and PD-1 was related to the distance of adjacent normal tissues to RCC (P<0.05). CONCLUSIONS The activation of PD-1 and TIGIT may exert negative regulatory effects and inhibit the immune response to cancer cells, resulting in immune escape of cancer cells. Both PD-1 and TIGIT may serve as potential targets for the treatment of RCC.