The Kelch-like (KLHL) family members consist of three domains: bric-a-brac, tramtrack, broad complex/poxvirus and zinc finger domain, BACK domain and Kelch domain, which combine and interact with Cullin3 to form an E3 ubiquitin ligase. Research has indicated that KLHL family members ubiquitinate target substrates to regulate physiological and pathological processes, including tumorigenesis and progression. KLHL19, a member of the KLHL family, is associated with tumorigenesis and drug resistance. However, the regulation and cross talks of other KLHL family members, which also play roles in cancer, are still unclear. Our review mainly explores studies concerning the roles of other KLHL family members in tumor-related regulation to provide novel insights into KLHL family members.