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Background: miRNAs and mRNAs have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop the pivotal miRNA biomarkers‐based prognostic signature for salivary adenoid cystic carcinoma. Methods: The miRNA and mRNA expression data were integrated from the gene expression omnibus database to study their involvement in salivary adenoid cystic carcinoma development and progression. Gene ontology and kyoto encyclopedia of genes and genomes were conducted to analyze the biological pathways. Reverse transcription‑quantitative PCR was used to verify the expression of selected miRNAs in salivary adenoid cystic carcinoma and corresponding normal tissues. Results: There were 386 differentially expressed genes: 158 upregulated and 228 downregulated genes and 102 differentially expressed miRNAs: 78 upregulated and 24 downregulated miRNAs in the salivary adenoid cystic carcinoma samples. A miRNA‐mRNA network containing 11 miRNAs and 199 genes was subsequently constructed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the genes targeted by the 11 miRNAs were mostly involved in tumor‐related pathways and processes, such as miRNAs in cancer, focal adhesion, neurotrophin signaling pathway, and the PI3K‐Akt signaling pathway. Among them, 4 miRNAs (miR‐375, miR‐494, miR‐34c‐5p, and miR‐331‐3p) were selected to verify by reverse transcription‑quantitative PCR in 36 pairs of collected salivary adenoid cystic carcinoma and adjacent nontumor samples. Overall survival analysis revealed that the higher expression of miR‐331‐3p was significantly associated with a worst overall survival and multivariate Cox regression analysis suggested that hsa‐miR‐331‐3p could be an independent prognostic factor for salivary adenoid cystic carcinoma. Conclusion: Our results revealed that 4‐miRNAs signature was a powerful prognostic biomarker for salivary adenoid cystic carcinoma, which provide a basis for exploring deeper mechanisms regarding the progression of salivary adenoid cystic carcinoma, and leading to the development of potential therapeutic strategies. [ABSTRACT FROM AUTHOR]