A limited number of studies have investigated the significance of cystatin C, creatinine, uric acid and urea in prostate cancer. The present study aimed to explore the correlation between these molecules and total prostate-specific antigen (tPSA) levels using big data from patients of different Chinese ethnicities. Patients undergoing physical examination at the Medical Examination Center of West China Hospital (Chengdu, China) between January 2010 and May 2019 were retrospectively included. A χ2 test or Fisher's test and Kruskal-Wallis rank-sum test were used to compare categorical and continuous variables. Pearson's correlation coefficients (r) with 95% CI were also determined to assess the correlation between tPSA and cystatin, uric acid, creatinine and urea in the entire patient population and in different ethnicities. A total of 253,281 male patients were included and their mean age was 47.83±14.28 years. The mean tPSA level of these patients was 1.15±1.88 ng/ml. The mean levels of the renal function-associated parameters cystatin C, uric acid, creatinine and urea were 0.91±0.19, 388.02±77.37, 83.94±55.89 and 5.23±1.23 ng/ml, respectively. In the total patient population, urea (r=0.0774, P<0.0001), creatinine (r=0.0219, P<0.0001) and cystatin (r=0.1513, P<0.0001) were slightly positively correlated with tPSA, whereas uric acid was negatively correlated with tPSA (r=-0.0307, P<0.0001). Subgroup analyses generally yielded consistent results; however, a stronger correlation was noted between cystatin C and tPSA for the Mongolian ethnicity (r=0.6572, P<0.0001) and between creatinine and tPSA for the Yi ethnicity (r=0.6125, P<0.0001). In conclusion, the present study used data from a large population to reveal a generally significant and slightly positive correlation between tPSA and cystatin C levels among the 10 most common ethnicities in China. Subgroup analyses indicated that the tPSA level was moderately positively correlated with the creatinine level for the Mongolian and Yi ethnicities and the cystatin C level was moderately positively correlated with tPSA for the Mongolian ethnicity. Future studies are required to confirm and expand the present results. Copyright © 2020, Spandidos Publications.