Objective: To investigate the expression levels and clinical significance of serum suppressor of cytokine signaling-3 (SOCS3) and associated cytokines in HIV/TB co-infected patients. Methods: The serum levels of SOCS3, IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17 and IL-22 were quantified by using enzyme-linked immunosorbent assays (ELISA) in 50 HIV-infected patients, 48 HIV/TB co-infected patients and 50 healthy donors. Pearson correlation analysis was used to analyze the correlation between SOCS3 and other seven cytokines. Results: Serum levels of SOCS3 expression in HIV/TB co-infection group were significantly higher than those in HIV-infection alone and the control group. There was also significant correlation between SOCS3 and IFN-γ, IL-4, IL-6, IL-10, IL-2 in HIV/TB co-infection group. Conclusions These findings indicated that SOCS3 may play an important role in the immune response of patients with HIV/TB co-infection and it may be helpful in the diagnosis of HIV/TB co-infection.