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Background: Clear cell renal cell carcinoma (ccRCC) is a malignant tumor most commonly seen in the urinary system, featuring quick progression, invasive behavior, frequent recrudesce, and bad prognosis, whereas Chondroitin polymerizing factor (CHPF) is an essential glycosyl transferase of biosynthesis involved chondroitin sulphate. But the relationship between the two has not been fully understood so far. The present research will probe into the relationship between CHPF and ccRCC. Methods: Explore the CHPF expression level in renal ccRCC tissues through bioinformatics analysis of The Cancer Genome Atlas (TCGA) and the real-time quantitative polymerase chain reaction detection system (qPCR); acquire relevant clinical data from the TCGA database and use Kaplan-Meier survival analysis to verify the relevance of CHPF expression to the clinical prognosis of ccRCC patients; then, effectively silence CHPF in ccRCC 786-O cells by a lentivirus-mediated approach; next, observe the effects of CHPF on tumor cell proliferation, cell cycle progression, and apoptosis. Results: In ccRCC tissues, CHPF expression has been significantly upregulated; the higher expression, the shorter survival of ccRCC patients. CHPF downregulation in the 786-O cell can effectively hold back the proliferation, apoptosis and cycle of cancer cells. Conclusion: Based on the above results, we arrive at a conclusion that CHPF expression contributes markedly to the development of human ccRCC cells. Therefore, CHPF may act as a potential prognostic marker of ccRCC and provide a new target for ccRCC treatment.