Objectives: To investigate the prevalence, incidence of abnormal liver function tests (LFTs), and mortality during anti-TB treatment in patients multi-infected with HIV, tuberculosis (TB), and hepatitis virus (hepatitis B virus (HBV) and hepatitis C virus (HCV)). Methods: Three hundred and sixty-one HIV-positive TB patients were enrolled and divided into an HIV/TB group, HIV/TB/HBV group, and HIV/TB/HCV group; 1013 HIV-negative TB patients were selected randomly as controls. Results: One hundred and seventeen (32.4%) HIV-positive TB patients were infected with HBV and/or HCV, compared with 90 (8.9%) HIV-negative TB patients (p = 0.000). HIV-positive TB patients had a higher incidence of anti-TB drug-induced hepatotoxicity than HIV-negative TB patients (4.2% vs. 1.0%, odds ratio (OR) 4.348, 95% confidence interval (CI) 1.935–9.769, p = 0.000). The incidence of abnormal LFTs in the HIV/TB/HBV group and HIV/TB/HCV group were significantly higher than in the HIV/TB group (40.7% vs. 11.1%, OR 5.525, 95% CI 2.325–13.131, p = 0.000; 20.0% vs. 11.1%, OR 2.009, 95% CI 1.057–3.820, p = 0.031). A total of 68.4% of patients with HBV-DNA >1.0 × 105 copies/ml and 42.9% of patients with HCV-RNA >1.0 × 105 copies/ml had abnormal LFTs. Twenty-three (19.7%) patients multi-infected with HIV, TB, and hepatitis virus died during anti-TB treatment. Conclusions: HIV, HBV, and HCV are risk factors for the development of abnormal LFTs and mortality during anti-TB treatment. TB patients co-infected with HIV and hepatitis virus need close follow-up.