This study evaluated microRNA-590-5P (miR-590-5P), which functions as an anti-onco-miRNA in TSCC by downregulating FasL expression.In this study, immunohistochemistry was used to detect FasL protein expression in 30 OSCC samples and 8 normal oral mucosa tissue samples. Target Scan was used to predict miRNAs that target FasL. Luciferase reporter assays were used to confirm the effects of miRNA on FasL. Subsequently, the SCC3 tongue cancer cell line was transfected with a miR-590-5P mimic or miR-590-5P inhibitor. qPCR and Western blots were used to detect the expression levels of miR-590-5P and FasL. SCC3 cell viability, apoptosis and growth were assayed by MTT assays, colony formation assays, and a xenograft model.FasL expression was significantly higher in OSCC tissue samples than in normal oral mucosa tissue samples. miR-590-5P could downregulate the expression of FasL in vitro via direct binding to its 3'-untranslated region (3'-UTR). Overexpression of miR-590-5P inhibited the proliferation of SCC3 cells. Moreover, miR-590-5P increased the sensitivity of SCC3 cells to the chemotherapeutic agent cisplatin (DDP) and led to a significant decrease in colony formation ability. The xenograft experiment confirmed that miR-590-5P can suppress the development of TSCC.These results suggest that miR-590-5P targets FasL to inhibit the development of tongue cancer and that miR-590-5P may be a novel therapeutic target for TSCC.