HIV-1 matrix protein p17 was found to be associated with lymphoma development in vitro. This study aimed to elucidate the pathogenetic roles of HIV-1 p17 in AIDS-related lymphoma.Expression of HIV-1 proteins p17, p24, nef and tat were evaluated in tumor tissue samples from 60 lymphoma patients and lymph node samples from 23 non-lymphoma patients with HIV-1 infection by immunohistochemistry. Microvascular density (MVD) determined by CD34 were also assessed in tumor tissues. Clinicopathological data of AIDS patients with lymphoma were collected retrospectively.The subtypes of lymphoma among sixty AIDS patients were diffuse large B-cell lymphoma (32 cases), Burkitt lymphoma (23 cases), Hodgkin's lymphoma (4 cases), and plasmablastic lymphoma (1 case). The expression rate of HIV-1 p17 in lymphoma and non-lymphoma group was 63 % (38/60) and 61 % (14/29) respectively, with no significant difference (p = 0.835). The positive expression rate of p17 in both groups was significantly higher than that of p24, nef and tat (p < 0.05). The expression of p17 was associated with a higher MVD in the lymphoma group (p < 0.05). There were no significant differences in the 2-years overall survival between p17 positive and negative group (61 % vs. 50 %, p = 0.525).The common expression of HIV-1 matrix protein p17 in both lymphoma and lymph node tissues of AIDS patients and the association between p17 expression and the higher MVD suggest that the accumulation and persistence of p17 in tissues may play a role in lymphoma development.