Purpose: The purpose of this study was to examine the effect of laughter therapy on depression, anxiety, fatigue, and quality of sleep in gastrointestinal cancer survivors. Methods: This study was a randomized controlled trial. We compared the effect of laughter therapy with usual care only in post chemotherapy gastrointestinal patients. Outcomes included changes in depression and anxiety (according to the Hospital Anxiety and Depression Scale), fatigue (according to the Fatigue Severity Scale), and quality of sleep (according to the Verran & Synder-Halpern Sleep Scale). Data was collected July 2015 through January 2016. Seventy nine participants who agreed to participate in this study were randomized to either the experimental group (n=40) or the control group (n=39). Therapy included eight sessions (60 minutes each, once weekly). Data were analyzed using the Windows SPSS 22.0 program. Results: Laughter therapy was effective in reducing fatigue (p=.019) and increasing satisfaction of sleep (p=.030). There were no differences between the groups after therapy for depression (p=.129) and anxiety (p=.200). Conclusion: Results of this study indicate that laughter therapy may be an effective nursing intervention for improving the health status of gastrointestinal cancer survivors after chemotherapy.