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Previous studies have reported that platelet count is associated with the progression of liver disease caused by hepatitis B virus (HBV), but there have been no reports on whether platelet count is associated with immune recovery in HIV/HBV co-infected patients. A retrospective analysis was conducted on 167 HIV-infected patients whose continuously highly active antiretroviral therapy (HAART) strategy was lamivudine +tenofovir+ efavirenz, of which 75 were HIV/HBV co-infected patients and 92 were HIV mono-infected patients. The biochemical examination results and demographic characteristics of all patients before HAART were collected, and routine blood test results (including platelet count) and immune cell count (including CD4 cells count) after all time points of HAART were obtained. All patients were observed until 72 months. CD4 cells count of 350 or 500 cells/μl 72 months after HAART served as the boundary for judging the immune reconstruction effect. The basic characteristics of HIV/HBV co-infected patients and HIV mono-infected patients were matched. All patients had a good viral response (HIV RNA <20 copies/ml, HBV DNA < 100 copies/mL) and immune response during HAART. The platelets with poor immune recovery in HIV/HBV co-infected patients were also maintained at an apparent lower level than that in patients with good immune recovery. However, this phenomenon was not found in HIV mono-infected patients. The platelet level at many time points after HAART therapy in HIV/HBV co-infected patients can predict the effect of immune recovery at 72 months after HAART. The platelet counts of HIV/HBV co-infected patients were correlated with CD4 counts during the follow-up of HAART. These results suggest that the mechanisms associated with thrombocytopenia may be involved in the regulation of immune recovery after treatment in HIV/HBV co-infected patients. • The platelet counts of HIV/HBV co-infected patients were correlated with CD4 counts during the follow-up of HAART. These results suggest that the mechanisms associated with thrombocytopenia may be involved in the regulation of immune recovery after treatment in HIV/HBV co-infected patients. • A long-term observational study was performed. • The antiviral therapy of all HIV-infected patients was lamivudine, tenofovir and efavirenz continuously. [ABSTRACT FROM AUTHOR]