Purpose <p>The present study was conducted to determine the relationship between neurotic personality traits and symptoms of post-traumatic stress disorder (PTSD) in breast cancer patients, with the mediation of self-efficacy and negative coping.</p> Methods <p>A cross-sectional study design was used. A total of 328 breast cancer patients admitted to two tertiary hospitals in Dali, China, from July 2023 to January 2024 were included. Participants completed the General Information Questionnaire, the PTSD Inventory-Civilian Version, the Social Support Rating Scale, the Brief Coping Styles Questionnaire, the General Self-Efficacy Scale, and the Eysenck Personality Questionnaire-Revised, short Scale for Chinese-Neuroticism. Data were analyzed using SPSS 26.0 and Mplus 8.8 software, binary logistic regression analysis, and weighted least squares estimation. Data were analyzed by SPSS 26.0 and Mplus 8.8 software, using binary logistic regression analysis and weighted least squares estimation.</p> Results <p>Employment status, time since diagnosis, neurotic personality traits, negative coping, and self-efficacy were correlates of the development of PTSD symptoms in breast cancer patients ( <i>P</i> &lt; 0.05). Neurotic personality traits in breast cancer patients had significant direct and indirect effects on PTSD symptoms (total effect: 0.625), and self-efficacy and negative coping were also mediated independently or in combination.</p> Conclusion <p>We suggest that healthcare workers pay close attention to the personality traits of breast cancer patients in their daily work, and take a series of effective targeted measures promptly for patients with neurotic personality traits to help them enhance their sense of self-efficacy and reduce their negative coping styles, to effectively improve the mental health of patients.</p>