Objective To investigate the expression of human cartilage glycoprotein-39 (YKL-40) and interleukin-6 (IL-6) in the tissues of prostate cancer. Methods From May 2016 to February 2018,42 specimens of prostate tissue from patients with prostate cancer who underwent radical surgery in the hospital were enrolled in the experimental group, and 38 operativepathological tissues from patients with benign prostatic hyperplasia were enrolled in the control group. The levels of YKL-40 and IL-6 expression in the tissue samples of the two groups were detected by Western blot and fluorescent PCR respectively. The positive expression rate of YKL-40 and IL-6 was detected by immunohistochemistry, and the correlation of YKL-40 and IL-6 with clinicopathologic features of prostate cancer was analyzed. Results Western blot results showed that the relative expression of YKL-40 and IL-6 protein in the experimental group was higher than that in the control group (P<0.05). The results of PCR showed that the relative expression of YKL-40 and IL-6 mRNA in the experimental group was higher than that in the control group (P<0.05). The positive expression rate of YKL-40 and IL-6 in the prostate cancer patients with stage III, lymph node metastasis and pathological grading with poor differentiation was higher than that in the prostate cancer patients with stage I~II, non-lymph node metastasis and pathological grading with highmoderate differentiation (P<0.05). The correlation analysis showed that the expression of YKL-40 and IL-6 in the tissues of prostate cancer was positively correlated (r=0.861, P<0.05). Conclusions The expression of YKL-40 and IL-6 protein is higher in prostate cancer and associated with clinicopathological features. YKL-40 and IL-6 protein can be used as clinical screening markers for prostate cancer.