The abnormal expression of miR-92a-3p was detected in multiple cancers. However, the biological role and underlying mechanism of miR-92a-3p in tamoxifen-resistant cells are still unknown. The main objective of our study was to find potential miR-92a-3p regulating pathways involved in tamoxifen resistance and to construct their regulatory network using bioinformatics. Four gene expression profiles were retrieved from GEO database and the GEO2R tool was used for analysis. GSE41922 and GSE42072 were applied to investigate aberrant miR-92a-3p expression in breast cancer serum and tissue. We found that miR-92a-3p expression was higher in breast cancer serum or tissue than in healthy volunteer serum or adjacent normal tissue, and high expression of miR-92a-3p could predict poor prognosis of breast cancer patients. In our qRT-PCR validation, we found that miR-92a-3p was upregulated in tamoxifen-resistant cells. MiR-92a-3p might play a role in tamoxifen resistance. In order to find the relationship between miR-92a-3p and some key genes and their potential molecular mechanisms in tamoxifen-resistant cells. The microarray data GSE26459 and GSE28267 were analyzed to determine the differentially expressed genes (DEGs) or miRNAs (DEMs). Furthermore, the related long non-coding RNAs (lncRNAs) were screened with starBase v2.0. Finally,microRNA.org,miRDB, targetminer and targetscan were applied to predict the targets of miR-92a-3p. Through analysis, we find that miR-92a-3p may be used as a potential biomarker for early detection of cancer and monitoring the efficacy of endocrine therapy.