Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1’s roles in different contexts of prostate cancer, with an emphasis on its crosstalk with diverse signaling pathways. Furthermore, we highlight the potential therapeutic strategies for cancers with dysregulated CHD1. At last, we discuss current research gaps in understanding CHD1’s biological functions and molecular basis during disease progression, as well as the modeling systems for biology study and therapeutic development.