Breast cancer is the most common global malignancy and the leading cause of cancer deaths for women. Aromatase inhibitors are clinically recommended therapy for the disorders. However, resistance to aromatase inhibitors therapies still occurs and the underlined molecular mechanisms are still poorly understood. The tumour specimens consisted of aromatase inhibitor-sensitive and aromatase inhibitor-resistant breast cancer patients, who were compared and the differentially expressed genes for aromatase inhibitor-sensitive patients were generated and related genetic network was explored. The enriched cellular process and signaling cassettes for aromatase inhibitor-sensitive patients were also in-depth investigated. Compared with the aromatase inhibitor-resistant patients, 896 genes showed a significant differential expression. 621 were significantly up-regulated and 275 were remarkably downregulated. From the interaction network, the differentially expressed genes including signal recognition particle 72, B-cell lymphoma-2 associated transcription factor 1, cathelicidin antimicrobial peptide and defensin alpha 1B could be considered as the key target genes for aromatase inhibitors treatment in breast cancer patients. These differentially expressed genes were enriched in processes involving immunoglobulin complex, cell division and others while, drug metabolism and other signalling mechanisms were enriched in aromatase inhibitors treatment of breast cancer patients. The study speculated several novel gene targets for aromatase inhibitors therapeutic treatment of breast cancer patients and initiated a beneficial direction for future aromatase inhibitors drug resistance research.