Abstract: Objective To evaluate the expression and prognostic value of superoxide dismutase 2 (SOD2) in breast cancer and explore its possible role in the occurrence and progression of breast cancer. Methods We performed bioinformatics analysis of the TCGA data for the expression and clinical relevance of SOD2 in patients with breast cancer. Gene enrichment analysis (GSEA) was performed using the KEGG gene set, the protein interaction network was constructed using the STRING database, and the key genes were screened using Cytoscape software. We also collected 60 pairs of primary breast cancer tissue samples and adjacent samples for detecting SOD2 expressions using immunohistochemistry and RT-qPCR and analyzed the correlation of SOD2 expression with the clinicopathological parameters of the patients. Results The expression of SOD2 was significantly lower in breast cancer tissue than in adjacent tissues with significant correlation with TNM stage and axillary lymph node metastasis (P<0.05). Kaplan-Meier survival analysis showed that the recurrence-free survival, distant metastasis-free survival (RFS) and post-progressive survival were significantly shorted in patients with high SOD2 expression than in those with low SOD2 expression (P<0.05). GSEA enrichment analysis indicated that SOD2 played an important role in the JAK-STAT signaling pathway. IL10 and STAT4 were identified as the key genes in the PPI network, and they were both positively correlated with SOD2. In the 60 pairs of clinical samples, SOD2 was highly expressed in breast cancer tissues with close correlation with axillary lymph node metastasis and the expressions of estrogen receptor and androgen receptor (P<0.05). Conclusion The expression of SOD2 in breast cancer is significantly correlated with TNM stage and axillary lymph node metastasis. SOD2 may affect the proliferation, invasion and metastasis of breast cancer cells possibly by regulating IL10 and/or STAT4 to affect the JAK/STAT signaling pathway.