Bip is a key chaperone of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, and controlling the activation of ER stress sensors. ER stress has been suggested to be involved in various diseases, such as diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. Recently, autoantibodies against Bip were detected in the sera from patients with prostate cancer and those with rheumatoid arthritis. In this review, we summarize recent findings concerning Bip and anti-Bip autoantibodies in cancer and autoimmune diseases.