Abstract: The present disclosure relates to a novel human antibody or an antigen-binding fragment thereof that recognizes the SMO (smoothened) protein as an antigen and binds specifically thereto. The antibody of the present disclosure binds specifically to the SMO protein, which is directly involved in major cancer progression processes such as proliferation, migration, invasion and metastasis of cancer cells, and blocks the progression those processes. Therefore, it can be usefully used as a therapeutic agent for various cancers such as colon cancer, etc., resistant cancer, metastatic cancer, or recurrent cancer.