OBJECTIVES: The purpose of this study was to assess the effects of laughter therapy on mood, stress and health-related quality of life (HRQoL) in patients treated with hemodialysis. METHODS: This is a randomized controlled intervention study. Briefly, forty hemodialysis patients attending a university hospital dialysis center were randomized (1:1) to either a laughter group or a control group without laughter therapy. A total of 11 patients completed the laughter therapy program and 18 patients in a control group were remained. Laughter therapy program was composed of weekly four group sessions and daily 15 seconds' of individual session by telephone for 4 weeks. The mood and stress were measured by visual analogue scale (VAS) and serum cortisol level, respectively, and HRQoL was evaluated by kidney disease quality of life short form version 1.3 (KDQOL-SFTM 1.3) before and after active laughter program. RESULTS: Mood measured by VAS was significantly improved in the active laughter therapy group (n=11) compared to a control group (n=18) (p<0.05), whereas changes in serum cortisol level was not significantly different between two groups. Role due to emotional, social functioning, and mental health quality of life scales improved significantly in the laughter group (all p's<0.05). In the kidney disease-targeted scales, symptom/problem and quality of social interaction scales were significantly improved in the laughter group (all p's<0.01). CONCLUSION: A Laughter therapy was an effective program for improving the mood and limitations of usual role activities due to emotional problems, mental health and social domains of quality of life in hemodialysis patients.