Abstract: Objective To analyze the efficacy of combined antiviral and anti-tuberculosis therapy in the treatment of initial pulmonary tuberculosis patients with positive hepatitis B virus deoxyribonucleic acid (HBV-DNA) and the correlation of interferon-γ(IFN-γ) and semi-quantitative scoring system (SSS) score with hepatic function.Methods A total of 120 initial pulmonary tuberculosis patients with positive HBV-DNA who were admitted to Rugao Hospital Affiliated to Nantong University from March 2022 to March 2023 were selected. According to the random number table method, they were divided into two groups (n=60):a control group and an observation group. The control group underwent conventional anti-tuberculosis therapy, while the observation group received antiviral therapy in addition to anti-tuberculosis therapy. All the patients were treated for six months. Both groups were compared for clinical efficacy, including lesion absorption, negative conversion of sputum culture, and HBV-DNA negative conversion, as well as hepatic function and inflammatory factors levels before and after treatment. The levels of IFN-γ, HBV-DNA and SSS scores at different time points (before treatment, and 1, 3 and 6 months after treatment) were compared between the two groups. The Pearson correlation coefficients of hepatic function with IFN-γ and SSS scores were calculated.Results The observation group showed higher proportions of patients with lesion absorption, negative conversion of sputum culture and HBV-DNA negative conversion than those in the control group (P<0.05). After treatment, increased levels of ALT, AST and TBiL and decreased levels of IL-2, IL-6, IL-8 and TNF- were seen in the two groups, compared with those before treatment, where the changes in the observation group were less obvious than those in the control group (P<0.05). Compared with those before treatment, the levels of IFN-γ increased after treatment for 1, 3 and 6 months, where the levels of IFN-γ in the observation group were lower than those in the control group, with statistical differences (P<0.05). Compared with those before treatment, the levels of HBV-DNA in the observation group gradually decreased after treatment for 1, 3, and 6 months, and those in the control group increased, where the levels of HBV-DNA in the observation group were lower than those in the control group (P<0.05). Compared with those before treatment, the levels of SSS scores increased after treatment for 1, 3 and 6 months, where the levels of SSS scores in the observation group were lower than those in the control group, with statistical differences (P<0.05). According to Pearson correlation analysis, IFN-γ levels were positively correlated with ALT, AST, TBiL and SSS scores in initial pulmonary tuberculosis patients with positive HBV-DNA (r>0, P<0.05). There was no statistical difference in the incidence of adverse reactions between the two groups (P>0.05).Conclusions Combined antiviral and anti-tuberculosis therapy can effectively improve the clinical outcome of initial pulmonary tuberculosis patients with positive HBV-DNA, reduce inflammation and HBV-DNA levels, avoid hepatic damage, and stabilize hepatic function, without increases in the risk of adverse reactions.