Skin cancer is the out-of-control growth of skin cells that can be divided into keratinocyte carcinoma (non-melanoma) and malignant melanoma. Basal cell carcinoma (BCC) and squamous cell carcinomas (SCC) are the most common forms of keratinocyte carcinoma that may grow to involve other parts of the body. These cancers are caused by exposure to ultraviolet (UV) light, toxic substances, and a family history of skin problems. Different signaling pathways are likely to be involved in skin cancer. The TP53 gene (the gene coding for cellular tumor protein p53) is among the most diverse and complex molecules involved in cellular functions. The p53 pathway can initiate DNA replication, modulate cell cycle events, and interact with tumor suppressor genes (TSGs). Mutations in TP53 can occur in numerous human cancers, leading to cellular immortalization, inappropriate proliferation, and genomic instability. TP53 plays a big role in both melanoma and non-melanoma skin cancers. Despite the intensive investigation to clarify the impact of TP53 mutations in the induction of skin cancer, much remains to be elucidated. In this mini-review, we will discuss the protective role of p53 as a bona fide tumor suppressor gene in human skin cancers.