〔Abstract〕 Objective To investigate the relationship between serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and benign prostatic hyperplasia (BPH) with histological inflammation. Methods A total of 93 patients with BPH and histological inflammation diagnosed by postoperative pathology in Foshan Gaomin Hospital Affiliated to Guangdong Medical University from January 2018 to March 2021 were included in the observation group, and 31 patients with BPH alone diagnosed by postoperative pathology were included in the control group. The levels of serum TNF-α and IL-6 and prostate volume (PV) in the two groups were compared, and the relationship between TNF-α and IL-6 and PV in the observation group was analyzed. The observation group was further divided into mild group, moderate group and severe group according to the severity of inflammation, with 31 cases in each group. The differences of TNF-α, IL-6 and PV in the three groups were compared, and the relationship between the above indexes and the severity of inflammation were analyzed. Results The serum TNF-α, IL-6 levels and PV in the observation group were significantly higher than those in the control group, the differences were statistically significant (P < 0.05). Serum TNF-α and IL-6 levels were positively correlated with PV in the observation group (R = 0.341, P = 0.000; R = 0.612, P = 0.000). The results of comparison of the levels of TNF-α, IL-6 and PV in serum were severe group > moderate group > mild group, and the pairwise comparison between the two groups, with statistical significance (P < 0.05). Serum TNF-α, IL-6 and PV levels were positively correlated with the severity of inflammation (R = 0.385, P = 0.000; R = 0.554, P = 0.000; P = 0.632, P = 0.000). Conclusion There is a close relationship between serum TNF-α and IL-6 levels and BPH with histological inflammation, namely, the higher the levels of TNF-α and IL-6, the larger the PV and the more severe the histological inflammation.