<p>To investigate the correlation between serum sex hormone levels and clear cell renal cell carcinoma(ccRCC). The clinical data of male patients diagnosed with ccRCC and with simple renal cysts in our hospital from 2017 to 2023 were collected. The basic clinical data and serum sex hormone levels, including luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol(E₂), prolactin (PRL), progesterone(P), and testosterone (T), were compared between patients with ccRCC and patients with simple renal cysts. A total of 56 male patients with ccRCC and 82 male patients with simple renal cyst were included in the study. There was no significant difference in age, height, weight, BMI, LH, PRL, P and T between patients with ccRCC and simple renal cyst. The levels of E₂ and FSH in patients with ccRCC were lower than those in patients with simple renal cysts, and the differences were statistically significant (<i>p</i> = 0.024, <i>p</i> = 0.001, respectively). Logistic regression analysis showed that E₂ level was negatively correlated with ccRCC (OR = 0.968, <i>p</i> = 0.027). The serum E₂ and FSH levels in patients with ccRCC are significantly lower than those in patients with simple renal cysts, and E₂ is negatively correlated with ccRCC, suggesting that E₂ and FSH may play a role in the occurrence and progression of ccRCC. The study implied the potential estrogen-based therapeutic strategies in ccRCC and further study is needed to explore its mechanism.</p>