1.1 Aim: Fibrosarcoma is a rare malignant tumor of subcutaneous tissue characterized by slow infiltrative growth and a high rate of local recurrence. The participation of microRNAs (miRNAs/miRs) in the pathogenesis of human diseases and the vital role of miR-145 in different types of cancer. However, the role of miR-145 in fibrosarcoma remains unclear. The present study aimed to investigate the effect of miR-145 in the progression of fibrosarcoma and its potential application as a new therapeutic target. 1.2. Methods: The present study screened out a differential gene named high mobility group protein A2 (HMGA2) via bioinformatics analysis. In the present study, the gene expression profiles of fibrosarcoma cells and normal cells were downloaded from GEO Datasets GSE10021 and GSE1774. The human fibrosarcoma cell line HT1080 were transfected with miR-145 mimics, mimic negative control (NC), pCMV6 vector, overexpression plasmid vector of HMGA2, (si)RNA-HMGA2 or siRNA-NC. Reverse transcription-quantitative PCR and western blot analysis were performed to examine the mRNA (miR-145) and protein (HMGA2, N-cadherin, Vimentin and E-cadherin) expression levels in HT1080 cells. Cell Counting Kit-8, wound healing and Transwell assays were used to examine the TH1080 cell viability, proliferation and migratory capacities, respectively. Bioinformatics prediction and luciferase reporter assay were performed to investigate the relationship between miR145 and its potential target gene (HMGA2). 1.3. Results: The results demonstrated that overexpression of HMGA2 promoted cell proliferation, migration and invasion of HT1080 fibrosarcoma cells, whereas HMGA2 knockdown had no effect on the proliferation of HT1080 fibrosarcoma cells. However, overexpression of miR-145 reversed the facilitating effects of HMGA2 in tumor progression via epithelial-to-mesenchymal transition (EMT) modulation. Mechanistically, miR-145 exerted its inhibitory role in fibrosarcoma by directly binding to the 3’-untranslated region of HMGA2. 1.4. Conclusion: miR-145 plays an inhibitory role in fibrosarcoma progression by directly suppressing HGMA2 expression and EMT progression. Thus, miR-145 may act as a potential therapeutic target for malignant fibrosarcoma therapy