BACKGROUND This study aimed to investigate the factors associated with non-adherence of prescribed treatment in patients with multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in Anhui Province, China. MATERIAL AND METHODS A cross-sectional survey was conducted in each designated hospital between March 2020 and May 2021. A structured questionnaire was designed to collect categorical characteristics and the historical data of the study participants. Non-adherence was determined from patient medical records and face-to-face interviews using the questionnaire at each designated hospital for MDR/RR-TB. RESULTS A total of 201 patients with confirmed sputum cultures positive for MDR/RR-TB were enrolled, 27.4% of whom were non-adherent to MDR/RR-TB treatment. In Anhui, MDR patients had a high incidence of adverse events, of which gastrointestinal reactions accounted for the majority. Absence of other chronic diseases (odds ratio (OR) 0.401; 95% confidence interval (CI) 0.203-0.791) and having no drug discontinuation (OR 0.040; 95% CI 0.018-0.091) were protective predictors of adherence. Patients with MDR/RR-TB with secondary education level and above and monthly family income of $309.4 USD or higher were more likely to follow the guidelines. Those who received anti-tuberculosis treatment and those who lived in suburban areas were less likely to adhere to the treatment. Binary-logistic regression indicated that the risk factor of non-adherence was drug discontinuation. CONCLUSIONS Low education level, place of residence, poor financial conditions, presence of other chronic diseases, discontinuation of medication, and frequency of anti-tuberculosis treatments were influential factors of adherence to MDR/RR-TB treatment.