Objective To analyze the drug resistance of Mycobacterium tuberculosis complex (MTBC) in West China Hospital of Sichuan University in recent years to provide reference for drug resistance monitoring and prevention strategies of tuberculosis in general hospitals. Methods The clinical strains of MTBC that performed drug susceptibility tests in West China Hospital of Sichuan University between January 2019 and December 2022 were collected. The drug susceptibility information of 13 anti-tuberculosis drugs, namely rifampicin, isoniazid, ethambutol, streptomycin, rifabutin, amikacin, kanamycin, ofloxacin, levofloxacin, moxifloxacin, para-aminosalicylic acid, ethionamide, and capreomycin, was collected and retrospectively analyzed. Results A total of 502 clinical strains of MTBC were included, and 366 of them were isolated from newly-treated patients while 136 form re-treated patients. The resistance rates of MTBC strains to the first-line anti-tuberculosis drugs in descending order were 28.69% (isoniazid), 19.72% (ethambutol), and 14.94% (rifampicin). Among the second-line drugs, the resistance rates to ofloxacin, levofloxacin, and moxifloxacin were 13.55%, 12.15%, and 11.95%, respectively. The resistance rates to amikacin, kanamycin, para-aminosalicylic acid, and ethionamide were all less than 10%. The resistance rates to streptomycin, capreomycin, and rifabutin were 17.53%, 13.55%, and 12.15%, respectively. The resistance rates to the remaining 12 anti-tuberculosis drugs except capreomycin of MTBC strains isolated from re-treated patients were higher than those of MTBC strains isolated from newly-treated patients, and the differences were statistically significant (P<0.05). The isolation rates of monodrug-resistant, polydrug-resistant, multidrug-resistant (MDR) and pre-extensively drug-resistant (pre-XDR) strains were 9.36%, 7.37%, 7.17%, and 7.77%, respectively. The isolation rates of strains with the four drug-resistant phenotypes generally showed a downward trend during the four years, and the changing trends were statistically significant (P<0.05). The isolation rates of MDR and pre-XDR strains from re-treated patients were higher than those from newly-treated patients, and the differences were statistically significant (P<0.001). Conclusion Tuberculosis drug resistance in West China Hospital of Sichuan University, which is a comprehensive tuberculosis-designated hospital, remained severe during the four years from 2019 to 2022, and the prevention of tuberculosis and the monitoring of drug resistance should be further strengthened.