Introduction: Cancer related fatigue, a problem often less understood and under-diagnosed. It is imperative to find non-invasive and non-pharmacological solutions for managing it. The aim of the study was to assess the effect of pranayama on reducing the level of Fatigue during External Radiation Therapy (ERT) among the patients in a selected cancer hospital of Guwahati, Assam. Materials and methods: The study adopted Quantitative evaluative approach; randomized pre-test post-test control group design. Simple random sampling technique without replacement was used and 84 cancer patients were equally divided in control group (42) and experimental group (42). The pre-test level of fatigue was assessed from both the groups and pranayama as intervention was given to experimental group. Result: Pranayama was found to be effective in patients receiving ERT. It was found that following pranayama, majority in experimental group 41 (97.6%) had mild level of fatigue whereas in control group 27 (64.3%) experienced severe level of fatigue. There is significant mean difference in the experimental group as compared to control group after the intervention of pranayama (t=17.99, df=41, p-value=<.001). Conclusion: Pranayama is found to be effective intervention in reducing fatigue among cancer patients receiving ERT.