Objective: To explore the clinical value of serum autoantibodies and human leukocyte antigen (HLA-B₂₇) molecular testing in Uygur patients with human immunodeficiency virus (HIV) infection. Method: A total of 727 HIV-infected Uygur patients who visited Kuche infectious diseases hospital during May 2016 to March 2017 were include in this study. The other 390 healthy people were enrolled as controls. Serum antinuclear antibodies (ANA), anti-cyclic citrullinated peptide (CCP) antibody, anti-extractable nuclear antigen (ENAs) antibody and HLA-B₂₇ molecule were tested. Result: Among 727 HIV-infected Uygur patients, 317 were males and 410 were females with mean age (35.52±13.44) years old. The mean duration of disease was (6.34±3.05) years. There were 697 (95.87%) patients receiving highly active antiretroviral therapy (HAART) with mean duration of treatment (5.52±3.47) years. The mean CD4⁺T cell count was (520±271) cells/μl in 202 HIV-infected patients, and mean virus load was (108 139±20 498) copies/ml in 20 HIV-infected patients. Rheumatic manifestations were recorded in 238 (32.74%) HIV-infected Uygur patients, mainly with dry mouth and dry eye (15.41%) , alopecia (9.90%) , arthralgia (8.94%) , ect. Compared with the health controls, positive ANA was more common in HIV infected Uygur patients (33.43% vs. 17.43%, P<0.001) with low titers (ANA titer:1∶100) . HIV-infected Uygur patients had higher positive anti-u1-RNP antibodies positive rate (1.10%), but lower anti-SSA antibodies positive rate (0.14%) and anti-CCP antibodies positive rate (0.28%). Patients with positive ANA in HAART group were significantly less than that in non-treatment group (32.71% vs. 50.00%, P=0.049). There were no correlations between ANA and duration of HAART, CD4⁺T cell counts and virus load (r values 0.061, 0.047, 0.121, respectively. P>0.05). Only one female patient was HLA-B₂₇ positive (0.14%), which was significantly lower than that in healthy controls (3.08%) (P<0.001). Also, only one patient was diagnosed with rheumatoid arthritis (RA). Conclusion Autoimmune manifestations are common in HIV-infected Uygur patients. Several autoantibodies are positive, but the coincidence of rheumatic diseases is rare. It′s noted that patients with autoimmune manifestations should be considered as a differential diagnosis of HIV infection.