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Purpose: This study aims to explore the mediating role of sense of coherence in the relationship of type C personality and depression among newly diagnosed breast cancer patients. Methods: A descriptive and correlational survey was conducted in 600 breast cancer patients aged ≥18 years from September 2018 to March 2019 in Zhengzhou, China. The demographic questionnaire, Cancer Behavior Scale, Sense of Coherence Scale and Hamilton Depression Scale were included in this study. Data analysis was performed by correlation analysis, multiple linear regression analysis, and structural equation modeling. Results: The valid questionnaires were 575 (effective response rate: 95.8%). The score of sense of coherence was negatively correlated with type C personality and depression (r = −0.41, P < 0.01; r = −0.58, P < 0.01); the score of type C personality and depression were positively correlated (r = 0.51, P < 0.01). The results of multiple linear regression analysis revealed that the effect of type C personality on depression was partly mediated by sense of coherence, which was confirmed by structural equation modeling. The mediation effect accounts for 45.2% (0.269/0.594) of the total effect. Conclusion: The results of this study revealed that sense of coherence as a partial mediating role is essential for reducing the influence of type C personality on depression. Early and targeted psychological interventions on sense of coherence are needed to alleviate the symptom of depression in newly diagnosed breast cancer patients. [ABSTRACT FROM AUTHOR]