Objective: To study the effective nursing strategies for esophageal cancer related fatigue after thoracotomy. Methods: Eighty-two cases of patients undergoing thoracotomy of esophageal cancer in our hospital were randomly divided into observation group (n=41) and control group (n=41). The observation group received comprehensive nursing and control group received routine nursing. Changes of fatigue grade were compared between the two groups, Piper fatigue scale scores were recorded, and both groups were followed for 3 months to observe the quality of life. Results: Degree of fatigue showed no significant difference between the two groups before nursing (P>0.05). After nursing, the degree of fatigue showed a decreasing trend, and the degree of fatigue in observation group was significantly lower (P<0.05); compared with those before nursing, the scores of emotion, feeling, cognition and emotion in observation group and the scores of cognition and emotion in control group were decreased significantly (P<0.05). The above scores of observation group were significantly lower than those of the control group (P<0.05); except the social function, the scores of other dimensions in observation group were significantly higher than those before treatment (P<0.05), and the scores of emotional function and overall health in observation group were significantly higher than the control group (P<0.05). Conclusion: The implementation of psychological, diet, relaxation and a series of comprehensive nursing according to the characteristics of cancer related fatigue after thoracotomy of esophageal cancer can reduce the degree of fatigue, and improve the quality of life.