The interfacial disorder is a general method to change the metal-oxygen compatibility and carrier density of heterostructure materials for ionic transport modulation. Herein, to enable high proton conduction, a semiconductor heterostructure based on spinel ZnFe2O4 (ZFO) and flfluorite CeO2 is developed and investigated in terms of structural characterization, fifirst principle calculation, and electrochemical performance. Particular attention is paid to the interfacial disordering and heterojunction effffects of the material. Results show that the heterostructure induces a disordered oxygen region at the hetero-interface of ZFO-CeO2 by dislocating oxygen atoms, leading to fast proton transport. As a result, the ZFO-CeO2 exhibits a high proton conductivity of 0.21 S cm−1 and promising fuel cell power output of 1070 mW cm−2 at 510 °C. Based upon these fifindings, a new mechanism is proposed by focusing on the change of O–O bond length to interpret the diffffusion and acceleration of protons in ZFO-CeO2 on the basis of the Grotthuss mechanism. This study provides a new strategy to customize semiconductor heterostructure to enable fast proton conduction.