Disclosed is a method for searching, identifying, or validating a marker CACNA2D1 of tumor-initiating cells. The method comprises a step of immunizing an animal using HEP-12 cells originating from a recurrent tumor and rich in originating cells. Also disclosed is a monoclonal antibody specially recognizing CACNA2D1 or antigen-binding fragments thereof, and the use thereof for treating or preventing tumors or diseases or conditions related to CACNA2D1.