Degradations of 2,4-dichlorophenol (2,4-DCP) using TiO2/UV photochemical and horseradish peroxidase (HRP) enzymatic treatments, as well as simultaneous photochemical enzymatic treatments, by combining these two processes were systematically investigated and compared. When free HRP was used in the simultaneous process, a negative synergetic effect was observed due to serious inactivation of the HRP caused by UV irradiation in the presence of TiO2. A hybrid catalyst system was then developed by in situ encapsulating HRP inside nanochambers of TiO2-doped hollow nanofibers through coaxial electrospinning. Such encapsulation effectively avoided UV-induced deactivation of the enzymes, thus the 2,4-DCP degradation efficiency was improved significantly as compared with the that using HRP or TiO2/UV either separately or simultaneously in free formation. Furthermore, the higher the concentration of 2,4-DCP, the more remarkable the enhancement achieved, such that a 90% removal ratio was obtained within only 3 h for the degradation of 10 mM 2,4-DCP using the integrated TiO2 HRP hybrid catalyst system. While the removal ratio obtained with dispersed TiO2/UV, TiO2 doped in PU hollow nanofibers, free HRP, combination of dispersed TiO2 and free HRP under UV, as well as the encapsulated HRP, were only 31.37%, 27.98%, 49.71%, 36.53%, and 58.32%, respectively. The hybrid catalysts system also showed excellent recycling capability and thermal stability.