Cutaneous melanoma is a malignant tumor with a high mortality rate. Ubiquitin-specific protease 41 (USP41) has recently been reported to be overexpressed in various malignancies. However, its role in melanoma remains unclear. Gene Expression Profiling Interactive Analysis (GEPIA) was used to perform pan-cancer analysis using data from the the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Melanoma tissue microarray (TMA), clinical patient tissues, and cells were used to explore USP41 expression profiles by immunohistochemistry (IHC), RT-qPCR or Western blotting. Small interfering RNAs (siRNAs) were used to knock down USP41 in melanoma cells. Cell proliferation, migration, and invasion were assessed using CCK-8, EdU staining, wound healing, and transwell assays, respectively. Cell apoptosis was detected by flow cytometry and TUNEL staining. GEPIA revealed that USP41 is highly expressed in most human cancers, including melanoma. USP41 is overexpressed in melanoma tumor tissues and cells. IHC showed that USP41 was positively stained in melanoma tissues and was significantly correlated with the TNM stage of melanoma. USP41 knockdown inhibited cell proliferation, migration, and invasion while promoting cell apoptosis and inhibiting phosphorylated PI3K, AKT, and mTOR in the PI3K/AKT signaling pathway. The results indicate that USP41 may play a carcinogenic role in melanoma partly via the PI3K/AKT signaling pathway, suggesting that USP41 may be an effective therapeutic target for the treatments of cutaneous melanoma.