MicroRNAs have been verified as critical regulators in the development of melanoma. MiR-33a-5p was significantly downregulated in melanoma. However, the specific role and regulatory mechanism of miR-33a-5p in melanoma were still unclear. The present study identified that miR-33a-5p was downregulated in melanoma tissues and cells, while SNAI2 was upregulated. MiR-33a-5p directly targeted SNAI2 and negatively regulated its expression in melanoma cells. Overexpression of miR-33a-5p repressed proliferation, migration, invasion, EMT and promoted apoptosis of melanoma cell in vitro, these effects were partially reversed by SNAI2 overexpression. In addition, miR-33a-5p impaired melanoma growth in vivo by inhibiting SNAI2. Mechanistically, miR-33a-5p repressed activation of the PI3K/AKT/mTOR pathway by targeting SNAI2. In conclusion, miR-33a-5p repressed the progression of melanoma by targeting SNAI2 via inactivation of the PI3K/AKT/mTOR signaling pathway, providing a potential molecular mechanism for the treatment of melanoma.