Objective To analyze the pathway model for the effect of intolerance of uncertainty on cancer-related distress in patients undergoing colorectal cancer surgery, so as to provide a theoretical basis for medical staff to further identify the negative emotions in patients with colorectal cancer after surgery and carry out accurate care. Methods A total of 484 postoperative patients with colorectal cancer were selected from 4 tertiary grade A hospitals in Shandong province using convenience sampling method.The general information questionnaire, Intolerance of Uncertainty Scale-12, Impact of Event Scale-Revised, Hospital Anxiety and Depression Scale, 10-item Connor-Davidson Resilience Scale were utilized for the investigation. Results The total score of intolerance of uncertainty was （31.81±7.17）, and the total score of cancer-related distress was （33.69±11.87）.Patients′ intolerance of uncertainty was positively correlated with cancer-related distress, anxiety and depression;cancer-related distress was positively correlated with anxiety and depression; resilience was negatively correlated with intolerance of uncertainty and cancer-related distress; anxiety and depression were negatively correlated with resilience（all P＜0.05）.The result of structural equation model showed that χ2/df=2.385,RMSEA=0.054,GFI=0.988,AGFI=0.956,NFI=0.992,CFI=0.996, and all the indicators meet the fitting standard. The result of the path analysis showed that the intolerance of uncertainty could directly predict cancer-related distress; anxiety and depression, resilience played a chain mediating role in the pathway of intolerance of uncertainty on cancer-related distress （all P＜0.05）. Conclusion The level of intolerance of uncertainty and cancer-related distress in postoperative patients with colorectal cancer is moderate.The intolerance of uncertainty among postoperative patients with colorectal cancer could positively predict cancer-related distress, and it could also affect the cancer-related distress through the chain mediation of "anxiety and depression-resilience".Medical staff should pay attention to patients′ negative emotions in time, and take intervention measures to mobilize patients′ inner driving force to reduce the distress of patients′ negative emotions.