Objective: To analyze the effect of diary psychological guidance on negative emotion and self-efficacy in patients with duodenal ulcer. Methods: From August 2016 to September 2018, 88 patients with duodenal bulbar ulcer admitted to Harrison International Peace Hospital were divided into study group and control group by random grouping method, 44 cases in each group. The control group was given traditional intervention, while the study group was given diary psychological guidance on the basis of the control group. Both groups were assessed by SAS and SDS, Pittsburgh Sleep Scale, SF-36 Quality of Life Scale and Self-efficacy Scale before and after intervention at the end of the second week. Results: After intervention, SAS and SDS of the study group were (51.3±2.0), (52.4±1.9) respectively, while those of the control group were (58.5±2.8), (59.3±3.1). There were significant differences between the two groups (t=15.278, 13.211, P < 0.05). The Pittsburgh sleep quality score, self-efficacy score and quality of life score in the study group were higher than those in the control group (t=7.892-24.031, all P<0.05). Conclusion The intervention of diary psychological guidance can improve the negative emotions such as anxiety and depression, and improve the self-efficacy of patients with duodenal ulcer.