Background The role of miR‐626 in oral squamous cell carcinoma (OSCC) was investigated by targeting RASSF4. Methods The miR‐626 and RASSF4 expression was detected in normal oral mucosa or OSCC tissues and OSCC or normal cells. The methylation status of RASSF4 was analyzed using methylation‐specific polymerase chain reaction (PCR). The cytoplasmic/nuclear ratios (C/N ratios) targeted by miR‐626 were examined using microarray, followed by a dual‐luciferase reporter assay. The subcellular localization of RASSF4 and miR‐626 in OSCC cells was determined using RNA fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC), respectively. Ca9‐22 and HSC2 cells were divided into mock, inhibitor NC, miR‐626 inhibitor, scramble, RASSF4 and miR‐626 mimic + RASSF4 groups, and then CCK‐8, Annexin V‐FITC/PI, wound healing, Transwell, qRT‐PCR and western blotting assays were performed. Results OSCC tissues and cells had increased miR‐626 expression and decreased RASSF4 expression. Patients with RASSF4 methylation had lower RASSF4 expression than those without methylation. In addition, a negative correlation between miR‐626 and RASSF4 was found in OSCC tissues, both of which were correlated with the pathological grade, pathological stage, lymph node metastasis and patient prognosis. MiR‐626 targeted RASSF4 in OSCC cells. Overexpressed RASSF4 inhibited the proliferation, invasion, migration and epithelial–mesenchymal transition (EMT) of OSCC cells, promoted cell apoptosis, and blocked the Wnt/β‐Catenin pathway, which was reversed by miR‐626 overexpression. Conclusions Inhibiting miR‐626 can regulate the biological characteristics of OSCC cells, including proliferation, invasion, migration, EMT and apoptosis, by targeting RASSF4, which may be related to the Wnt/β‐Catenin pathway.