Herein, based on two large cohorts with 403 cases in total, we analyzed the expression pattern of HHLA2 and its clinical significance in ccRCC, and found that the positive rate of HHLA2 expression in ccRCC was over 40% and that of HHLA2 (+) was associated with shorter PFS and OS, in line with previous literature. This evidence concerns the gene HHLA2 and nonpapillary renal cell carcinoma.