Objective: To explore the correlation and clinical significance of whole blood lymphocyte subsets and the expression of Ki-67, p16, VEGF and CD34 in male condyloma acuminatum (CA) patients with human immunodeficiency virus (HIV). Methods: The clinicopathological data of 85 male patients with CA from October 2018 to October 2020 were retrospectively analyzed. They were divided into a CA group (36 cases) and a CA combined with HIV group (49 cases) according to whether they were infected with HIV. The infection of HPV and the count of helper T lymphocyte subsets (lymphocyte, T lymphocyte, CD4⁺T lymphocyte and CD8⁺T lymphocyte) in the whole blood of the 2 groups were analyzed; the pathological features of CA tissues were observed by HE staining; the expression of Ki-67, p16, VEGF and CD34 in CA tissues were detected by immunohistochemical staining; the expression differences of Ki-67, p16, VEGF and CD34 between the 2 groups were analyzed. Spearman rank-correlation analysis was used to analyze the correlation between the whole blood helper T lymphocyte subsets and HPV infection, Ki-67, p16, VEGF, CD34; logistic stepwise regression analysis was used to explore the influencing factors of CA complicated with HIV. Results: The CD8⁺T lymphocyte count, Ki-67 proliferation index, p16 expression, VEGF expression and CD34 microvessel density of the CA combined with HIV were higher than those of the CA group (P<0.001, P=0.009, P<0.001, P<0.001, P<0.001, respectively). The CD4⁺T lymphocyte count of the CA combined with HIV was lower than that of the CA group (P<0.001). There was no significant difference in HPV infection, lymphocyte count and T lymphocyte count between the 2 groups (P=0.135, 0.862 and 0.876). There was a positive correlation between lymphocyte count and Ki-67 proliferation index (r_s=0.257, P=0.018), a negative correlation between CD4⁺T lymphocyte count, p16 expression and VEGF expression (r_s=−0.232, P=0.033 and r_s=−0.252, P=0.020), and a positive correlation between CD8⁺T lymphocyte count and HPV infection, Ki-67 proliferation index, p16 expression and VEGF expression (r_s=0.220, P=0.043; r_s=0.346, P=0.001; r_s=0.350, P=0.001 and r_s=0. 363, P=0.001). Logistic regression analysis showed that CD4⁺T lymphocyte count, p16 expression, VEGF gene expression and CD34 microvessel density were independent risk factors for CA complicated with HIV. Conclusion: In CA male patients with HIV, the decrease of CD4⁺T lymphocyte count, the active proliferation of epithelial cells, and the increase of angiogenesis in the CA tissues can be used as important indicators for the diagnosis and poor prognosis of CA.