Objectives: To investigate the impact of anxiety sensitivity (AS) on regional spontaneous neural activity in patients with breast cancer and to explore the interplay among brain activity, AS, and health anxiety-related metacognition (MC). Methods: Sixty-four breast cancer patients (33 with high AS[HAS-BC], 31 with low AS[LAS-BC]) and 42 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging(rs-fMRI). Regional homogeneity (ReHo) was calculated and analyzed using one-way analysis of variance (ANOVA), followed by post hoc analysis (Gaussian random field correction, voxel-level p < 0.001, cluster-level p < 0.05). Correlations between ReHo values and clinical scores (Anxiety Sensitivity Index-3 [ASI-3], Metacognitions Questionnaire-Health Anxiety [MCQ-HA], and Generalized Anxiety Disorder 7-item scale [GAD-7]) were examined. A mediation model was constructed to investigate relationships among neural activity, AS and health anxiety-related MC. Results: Eight brain regions exhibited significant ReHo differences among the three groups: left pons, right inferior temporal gyrus (ITG), left middle temporal gyrus, right cerebellum lobule 4 and 5, right insula, right superior frontal gyrus, left postcentral gyrus, and right supplementary motor area. In breast cancer patients, ReHo in the right ITG was negatively correlated with MCQ-HA scores (r = -0.395, p = 0.0012). Mediation analyses revealed that ReHo in the right ITG mediated the relationship between ASI-3 and MCQ-HA scores (indirect effects = 0.111, 95 % CI [0.027, 0.238]). Conclusions: Altered spontaneous brain activity characterizes breast cancer patients with different levels of AS. Specifically, decreased ReHo in the right ITG mediates the relationship between AS and health anxiety-related MC in breast cancer patients.