This study aimed to screen potential microRNAs (miRNAs) and genes related to human primary breast cancer. The gene and miRNA expression profile data of GSE19783 was obtained from Gene Expression Omnibus. The matched messenger RNA (mRNA) and miRNA expression profiles of 100 human primary breast cancer samples were chosen for further analysis. The miRNA-gene regulatory modules were screened via iterative multiplicative updating algorithm. The potential functions of genes in modules were predicted by functional and pathway enrichment analysis; meanwhile, the potential functions of miRNAs were predicted by functional enrichment analysis. Furthermore, miRNA-miRNA functional synergistic network and miRNA-miRNA co-regulatory network were constructed. Totally, 16 miRNA-gene modules were screened, containing 222 miRNA-gene interactions. The genes in these modules were mainly related to breast cancer. Genes in module 6 (e.g., SFRP1) were enriched in cell junction assembly; genes in module 8 and 12 (e.g., ESR1 and ERBB4) were significantly implicated in mammary gland alveolus and lobule development. Meanwhile, genes in module 12 (e.g., ERBB4) were enriched in the pathway of endocytosis. Besides, several miRNAs (e.g., miR-375) were enriched in inflammatory cell apoptotic process; some other miRNAs (e.g., miR-139-5p and miR-9) were enriched in response to vitamin D. Additionally, miR-139-5p with several other miRNAs (e.g., miR-9) co-regulated SFRP1; miR-375, miR-592, and miR-135a co-regulated ESR1 and ERBB4. Some miRNAs (e.g., miR-139-5p and miR-9) and their target gene SFRP1, as well as several other miRNAs (e.g., miR-375, miR-592, and miR-135a) and their target genes (e.g., ESR1 and ERBB4), might be crucial in the pathogenesis of primary breast cancer.