Previous studies have explored the functions of microRNA (miR)-146a in different types of cancer through mediating different targets. However, the roles of miR-146a in malignant melanoma (MM) cell migration and invasion remain largely elusive. In the present study, the potential molecular function of miR-146a in MM was investigated. Reverse transcription-quantitative polymerase chain reaction was utilized to detect miR-146a expression in MM tissues and cell lines. A Transwell assay was performed to confirm the ability of migration and invasion. A luciferase assay and biological analysis were used to predict and determine the targets of miR-146a. The expression of miR-146a was upregulated in melanoma tissues and cell lines. Clinicopathological analysis indicated that the miR-146a level was negatively correlated with the progression of melanoma. Abnormal expression of miR-146a promoted cell migration and invasion in MM cells. Additionally, it was also observed that Mothers against decapentaplegic homolog 4 (SMAD4) was a novel target of miR-146a in MM. SMAD4 was negatively associated with miR-146a in MM and abnormal expression of SMAD4 attenuated miR-146a-mediated promotion of cell migration and invasion. In conclusion, miR-146a functioned as an oncogene by directly targeting SMAD4 and it may be a novel diagnostic and therapeutic marker of MM.