This study aimed to explore the role and regulatory mechanism of hsa-miR-147b in lung squamous cell carcinoma (LUSC) through The Cancer Genome Atlas (TCGA) database. The expression and clinical value of miR-147b in LUSC were analyzed in the TCGA database. The target genes of miR-147b were screened via miRWalk 2.0 and verified in TCGA database. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyzed the differential target genes of miR-147b. Kaplan-Meier survival analysis and Cox regression were used to screen the prognosis-related target genes. The expression of miR-147b in LUSC tissues increased, and was associated with poor prognosis, gender, and stage of LUSC patients. The area under the curve (AUC) of miR-147b was 0.8478 by the receiver-operating characteristic curve. There were 428 differentially expressed genes of miR-147b that played a critical role in drug transport, DNA binding, calcium signaling pathway, and Ras signaling pathway through GO and KEGG. , , , , , and were independent risk factors for poor prognosis in LUSC patients. LUSC patients in the high-risk group had a higher risk of death. The time-dependent AUC was 0.673. MiR-147b might be a potential molecular marker for poor prognosis in patients with LUSC.