Regulator of G‑protein signaling 1 (RGS1) has been found to be a critical factor in melanoma and other malignancies. However, the mechanism involved in the RGS1‑mediated promotion of melanoma progression is not clear. We based our study on samples collected from pathological specimens of melanoma patients. We found by immunohistochemistry that RGS1 expression was significantly higher in melanoma than that noted in nevus tissue (P<0.05). Kaplan‑Meier analysis demonstrated a significant correlation between increased RGS1 expression and reduced disease‑specific survival (P<0.05). RGS1 expression was also found to be related to the proliferation and migration of melanoma cells. RGS1 was able to bind to the Gαs in immunoprecipitation, but this interaction did not accelerate GTP hydrolysis in our experiment. Furthermore, we found that RGS1 may promote melanoma progression through the downstream effects of Gαs signaling, such as the increased phosphorylation of AKT and ERK by western blotting. Our results demonstrated that RGS1 promotes melanoma progression through regulation of Gαs‑mediated inactivation of AKT and ERK. Therefore, RGS1 is a novel therapeutic target for melanoma treatment.