The performance of a composite material system depends critically on the interfacial characteristics of the reinforcement and the matrix material. In this study, the interfacial shearing strength (IFSS) of a composite with an epoxy matrix and a novel carbon nanotube/carbon fiber (CNT/CF) multi-scale reinforcement was determined by single fiber-microdroplet tensile test, and the interfacial reinforcing mechanisms of the composite were discussed. Results show that the IFSS of the epoxy composite reinforced by CNT/CF is as high as 106.55 MPa, which is 150% higher than that of the as-received T300 fiber composite. And the main interfacial reinforcing mechanisms of this novel composite could be interpreted as chemical bonding, Van der Waals binding, mechanical interlocking, and surface wetting.