Disclosed is an anti-HB-EGF antibody having an internalizing activity. Preferably, a cytotoxic substance is bound to the anti-HB-EGF antibody. Also disclosed are: a cancer therapeutic agent and a cell proliferation inhibitor, each of which comprises the antibody as an active ingredient; and a method for treating cancer and a method for diagnosing cancer, each of which is characterized by administering the antibody. The types of cancer which can be treated with the cancer therapeutic agent include pancreatic cancer, liver cancer, esophageal cancer, melanoma, colorectal cancer, gastric cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, brain tumor and hematological cancer.