Objective To explore the status of decision fatigue and its influencing factors among surrogate decision makers of patients with advanced cancer, so as to provide a reference for developing targeted nursing interventions. Methods A total of 192 surrogate decision makers of patients with advanced cancer were investigated by utilizing a general information questionnaire, the Decision Fatigue Scale (DFS), and the Intolerance of Uncertainty Scale-12 (IUS-12). Results The participants scored 13.00 (11.00, 16.00) in DFS. Multiple linear regression analysis showed that, educational background, family financial burden, duration of diagnosis, and the score of IUS-12 were the main influencing factors of the participants′ decision fatigue (all P<0.05). Conclusion The decision fatigue among surrogate decision makers of patients with advanced cancer is in a moderate level. Healthcare providers should take targeted interventions based on the influencing factors to reduce the decision fatigue of surrogate decision makers.