Background: HIV-associated lymphoma is the most common subtype of HIV-associated cancers, with a very low incidence. To date, there are only few retrospective studies analyzing the clinical features and prognosis of HIV-associated lymphoma. Therefore, we performed a study to analyze the clinical characteristics and outcomes of newly diagnosed HIV-associated lymphoma patients in our center, as the largest HIV-associated lymphoma cohort in China so far. Methods: Totally 107 newly diagnosed HIV-associated lymphoma patients in Chongqing University Cancer Hospital, Southwest China, from July 2008 to August 2021, were analyzed. Results: In the 107 HIV-associated lymphoma cases, median age was 49 years (range: 23–87 years), and more patients were male (87.9%). Most patients had elevated lactate dehydrogenase (LDH) (78.5%), elevated β₂-MG (91.6%), advanced Ann Arbor stage (73.8%) and high IPI score (IPI score: 3-5) (62.7%) at diagnosis. Totally 46 patients (43%) had one or more sites of extranodal involvement, of whom 24 (22.4%) possessed two or more extranodal sites. Median CD4⁺ T cell count at diagnosis was 191/μl (range: 4-1022); 84 patients (78.5%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. Of the 72 patients evaluated at the end of treatment, the overall response rate (ORR) was 81.9% (59/72); 29 (40.3%) cases achieved complete response (CR), 30 (41.7%) had partial response (PR) and 9 (12.5%) experienced progressive disease (PD). In 99 HIV-associated lymphoma cases with complete follow-up data (median follow-up of 44.5 months [range: 2-160 months]), median PFS and OS were 36.0 months and not reached, respectively. The overall 5-year PFS and OS rates were 46.9% and 53.4%, respectively. Compared with individuals not administered anti-lymphoma treatment or administered less than 3 cycles anti-lymphoma therapy, those who received standardized anti-lymphoma therapy (≥3 cycles) showed improved PFS (p=0.0006) and OS (p<0.0001). In patients administered systemic anti-lymphoma therapy, the overall 2-year PFS rates for chemotherapy and R-chemotherapy were 29.5% and 67.1%, respectively (HR=0.44, 95%CI 0.210-0.927; p=0.020). The overall 2-year OS rates for chemotherapy and R-chemotherapy were 51.9% and 73.1%, respectively (HR=0.42, 95%CI 0.183-0.969; p=0.042). Conclusions: Overall, these data indicated that HIV-associated lymphoma has aggressive characteristics, including advanced Ann Arbor stage, high IPI score, more extranodal involvement and elevated LDH. Survival is significantly improved due to the wide use of cART and chemoimmunotherapy. Standardized anti-lymphoma therapy is significantly associated with superior outcomes. Clinical trial information: ChiCTR2100054581.