The purpose of this article is to describe the incidence of hand-foot syndrome (HFS) and self-management of patients with it, including their self-recognition, supportive care, and outcome at home. Study participants were patients with colorectal cancer (CRC) who received adjuvant chemotherapy after surgery. About 67% of participants had HFS, most at grade 1. The median chemotherapy cycle where HFS first appeared was cycle 2. The majority of patients knew nothing about how to alleviate HFS, and they used no methods to treat it. HFS can worsen the quality of life of patients with CRC receiving adjuvant chemotherapy. The incidence of severe-grade HFS was relatively high in the current study, and patients showed poor self-recognition and self-management. Nurses play a key role in educating patients on how to recognize HFS and use self-management techniques.