Melanoma is the second leading invasive cancer with a greater capacity to invade and metastasize. Increased oxidative stress has been shown to be involved in melanoma growth and spread. Several antioxidants, vitamins, and other phytochemicals have been shown to prevent melanoma cancer growth. However, the chemopreventive efficacy of vialinin-A, an edible mushroom-derived p-terphenyl antioxidant, on cancer growth and invasion is unknown. We, therefore, hypothesized that with its potent anti-oxidative and anti-inflammatory actions, vialinin-A could prevent melanoma cell growth and invasion. B16-F10 melanoma cells were treated without or with various concentrations of vialinin-A. The cell viability was determined by MTT assay and apoptosis by annexin-V staining. Our results suggest that vialinin-A prevents melanoma cell growth in a dose-dependent manner. Vialinin-A also prevents the invasion and migration of melanoma cells. Further, vialinin-A prevents the generation of reactive oxygen species and promotes apoptosis of B16-F10 cells. In addition, vialinin-A increases the activation of caspase-3 and cleavage of PARP protein. Vialinin-A also regulated the expression of various anti-apoptotic, pro-apoptotic, and inflammatory markers in melanoma cells. In conclusion, our results suggest that vialinin-A, through regulating oxidative stress-modulated apoptotic pathways, could prevent melanoma cell growth and invasion and has potential chemopreventive properties.