Hand-foot syndrome (HFS) is a relatively common, dose-limiting dermatologic toxic reaction associated with multiple chemotherapeutic agents, including pegylated liposomal doxorubicin (PLD). Early symptoms of HFS include erythema, marked discomfort, swelling, and tingling on the palms and soles of the feet, which may progress to blistering and even ulceration in severe cases. We report a case of a breast cancer patient who developed HFS after receiving 3 cycles of PLD. The patient presented with redness, swelling, blistering, ulceration, and exudation in her palms, soles, axillae, groin, and waist. After symptomatic treatment, her HFS symptoms were significantly relieved. At the same time, we have also examined the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data for further reports of the relationship between different anthracyclines and risk of HFS.