Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair, leading to hypersensitivity to ultraviolet (UV) sunlight and predisposes to various cutaneous and non-cutaneous malignancies. Platinum compounds are used against cutaneous cancers as concurrent chemoradiotherapy. But the XP gene polymorphism has a potential role in metabolism of these agents and their susceptibility. Here, we report a case of cutaneous squamous cell carcinoma in a patient with XP who had severe toxicity to chemotherapy. We also discuss other similar cases reported in literature of this entity, to highlight this potentially lethal pharmacogenomic association.