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Objective To investigate the influence of social support (including financial, treatment, and informational support) and medication use motivation on treatment adherence among multidrug-resistant tuberculosis (MDR-TB) patients. Methods From April to July 2022, 217 MDR-TB outpatients were selected via convenience sampling from three designated TB hospitals in Guizhou Province. Data were collected through face-to-face interviews using a self-designed questionnaire. Patients’ motivation for medication use was assessed using a 16-item scale. Patients were categorized into adherence and non-adherence groups based on treatment interruptions or missed doses. Unconditional binary logistic regression was employed to analyze the impact of social support and medication use motivation on treatment adherence. Path analysis explored the mediating role of medication use motivation in the relationship between social support factors and treatment adherence. Results Non-adherence to treatment was observed in 48.4% of patients. Adjusting for confounders, higher annual household income (OR=3.361, 95%CI: 1.672-6.947), family supervision of medication (OR=2.342, 95%CI: 1.177-4.766), and greater motivation for medication use (OR=1.405, 95%CI: 1.254-1.601) were positively associated with treatment adherence. Mediation analysis indicated that motivation for medication use mediated the relationship between social support factors (income and family supervision) and treatment adherence. Conclusion Providing financial assistance to low-income MDR-TB patients and utilizing family supervision during treatment are recommended. Additionally, enhancing health education to boost patients’ motivation for medication use can effectively improve treatment adherence. [ABSTRACT FROM AUTHOR]