This study described the prevalence of psychological distress and examined the moderating effect of self-esteem in the relationship between perceived discrimination and psychological distress among Chinese pulmonary tuberculosis (TB) patients. Seven hundred and twenty patients with TB from three cities of Shandong Province in eastern China participated in a cross-sectional survey. Patients were measured with the Kessler 10 (K10), the Rosenberg self-esteem scale, and a self-developed perceived discrimination questionnaire. A total of 58.6% of patients with TB scored above 16 on the K10, indicating moderate and serious psychological distress. Chi-square test revealed that female patients reported higher psychological distress than male patients. The structural equation modeling (SEM) analysis among the whole sample indicated that perceived discrimination was significantly related with psychological distress (β = .28, p ≤ .01). The multiple group analysis of SEM showed that perceived discrimination had a significantly substantial (β = .50, p ≤ .001), significantly moderate (β = .15, p ≤ .01), and insignificant effect (β = .05, p ≥ .05) on psychological distress among low self-esteem, moderate self-esteem, and high self-esteem patients with TB, respectively, which verified the moderating effect of self-esteem in the relationship between perceived discrimination and psychological distress.