Objective To investigate the drug resistance and drug resistance genes in human immunodeficiency virus (HIV) -infected patients with pulmonary tuberculosis (TB) in Zhengzhou, Henan province, so as to provide reference for effective diagnosis and treatment of HIV infection complicated with TB. Methods 3 270 registered HIV-infected (and) or TB patients in Zhengzhou, Henan province were screened for tuberculosis between January 2018 and December 2020. The epidemiology, drug resistance and drug resistance genes were studied. Results The incidence of HIV infection complicated with TB was 6.27%. Among the HIV-infected patients with TB, the majority patients were under 30 years old, 47.80% of the patients were infected with HIV through sexual transmission, 62.93% received not longer than 6 months of anti-tuberculosis treatment, 11.22% had delayed treatment, and 62.93% were initially treated for TB. The drug resistance rate was 45.37%, and mainly to isoniazid (15.12%), rifampicin (11.22%), and streptomycin (8.29%). A total of 103 drug-resistant strains were detected, and the rpoB gene mutation rate was 57.28%. katG and/or inhA gene mutations, with a mutation rate of 39.81%. Conclusions The risk of HIV infection with TB is high in Zhengzhou, Henan Province. Young adults are high-risk groups. Most of them receive short-term anti-TB treatment and initial treatment of TB. The distribution of drug resistance and drug resistance genes in HIV infected patients with TB is similar to those patients with simple TB. It is recommended to strengthen screening and prevention and control of high-risk groups in this area. If necessary, treatment plans for these groups can be developed based on drug resistance spectrum of TB.