A novel photoenzymatic catalytic system employing hollow ferrite nanotubes and horseradish peroxidase (HRP) has been developed to significantly enhance the conversion of methane to liquid-phase oxygenates. The 1.5 % HRP-Fe3O4 HNTs demonstrated an exceptional liquid product yield of 177.87 μmol g−1 h−1 and exhibited reusability for methane photo-oxidation under ambient conditions. The physicochemical characterization revealed that the immobilization of HRP enhanced the visible light absorption and charge carrier separation efficiency. The Fe3O4 HNTs facilitated methane (CH4) molecule adsorption, while photogenerated electrons and H2O2 participated in the Fe2+-porphyrin and Fe3+-porphyrin cycle of HRP, enabling continuous generation of hydroxyl radicals, which activated CH4 to methyl radicals. In situ EPR and FTIR results indicated that CH3OH and CH3CH2OH were produced via the formation and consumption of •CH3O and •CH2 intermediates. This work presents an efficient strategy and provides new insights into the direct photo-oxidation of methane reaction through a photoenzyme catalytic system.