The invention discloses an operating knife with a blade replaceable. The operating knife comprise a knife handle and the blade; the blade is divided into a fixed blade end and a detachable blade end, the fixed blade end is fixedly connected with the knife handle and detachably connected with the detachable blade end, the fixed blade end is internally provided with an elastic layer which is internally provided with multiple square holes, the detachable blade end is provided with multiple tooth parts matched with the square holes, and the tooth parts comprise the outer side tooth parts and the inner side tooth parts; the tail end of the blade is provided with a pointed end, a knife edge part is arranged on the inner side of the pointed end and comprises a tip part, an inner concave part and a smooth part which form the shape of S, one end of the fixed blade end is fixed inside the knife handle, the length of the part, making contact with the knife handle, of the fixed blade end is larger than one third of the whole length of the fixed blade end. The operating knife has the advantages of being simple in structure, rapid in incising, higher in efficiency and capable of saving operating time, decreasing the amount of bleeding and relieving pain of patients.