Abstract: Fibronectin type Ⅲ domain containing protein 3B （FNDC3B） localize to the endoplasmic reticulum （ER） membrane， where it maintains ER homeostasis and participates in the ER stress. Recently， the emerging evidence revealed that FNDC3B plays the multifaceted roles in the pathogenesis and progression of malignant tumors via regulating cancer cell apoptosis， proliferation， migration and invasion. These findings suggested FNDC3B may serve as both a potential diagnostic/prognostic biomarker and a therapeutic target in oncology. The gene and protein structure of FNDC3B， pathophysiological functions， and the molecular mechanisms underlying the development of various malignancies were comprehensively summarized. Furthermore， the new insights into future strategies were offered for tumor diagnosis， treatment and prognosis assessment.