The expression of hypoxia-inducible factor1alpha (HIF-1alpha) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1alpha was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. Invivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1alpha (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1alpha, suggesting it may be a potential therapeutic target for melanoma treatment.