Protein 4.1B/DAL‑1, encoded by erythrocyte membrane protein band 4.1‑like 3 (EPB41L3), belongs to the protein 4.1 superfamily, a group of proteins that share a conserved four.one‑ezrin‑radixin‑moesin (FERM) domain. Protein 4.1B/DAL‑1 serves a crucial role in cytoskeletal organization and a number of processes through multiple interactions with membrane proteins via its FERM, spectrin‑actin‑binding and C‑terminal domains. A number of studies have indicated that a loss of EPB41L3 expression is commonly observed in lung cancer, breast cancer, esophageal squamous cell carcinoma and meningiomas. DNA methylation and a loss of heterozygosity have been reported to contribute to the downregulation of EPB41L3. To date, the biological functions of protein 4.1B/DAL‑1 in carcinogenesis remain unknown. The present review summarizes the current understanding of the role of protein 4.1B/DAL‑1 in cancer and highlights its potential as a cancer diagnostic and prognostic biomarker in cancer therapeutics.