Objectives: Cancer is an increasingly important cause of morbidity and mortality among patients undergoing hemodialysis (HD). Although β-blockers have been suggested to exert potential anticancer effects through pleiotropic mechanisms, evidence in HD populations remains limited. Methods: Using nationwide data from the Korean Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of adult patients receiving maintenance HD. β-blocker exposure was defined as ≥ 60 cumulative days of β-blocker prescription within a 1-year. Incident cancer and post-diagnosis survival were evaluated. Results: Among 58,822 HD patients, 25,152 were classified as β-blocker users. During a mean follow-up of approximately 5 years, overall cancer incidence did not differ between β-blocker users and non-users. Five-year cancer-free rates were comparable in both the total and propensity-matched cohorts. However, post-cancer diagnosis survival was lower among β-blocker users. In cancer-specific analyses, β-blocker use was associated with a higher incidence of lung and renal cancers, whereas risks for other major cancers did not differ significantly. Conclusion: β-blockers use was not associated with overall cancer incidence. However, β-blocker use was associated with a higher risk of renal and lung cancer and appeared to be linked to poorer overall survival among patients with cancer. Given the limitations of the study, establishing a robust causal relationship between β-blocker therapy and cancer development or cancer-related survival in patients undergoing HD remain challenging.