Abstract: The silk fibroin (SF) nanofibers were prepared by electrospinning with rich domestic silk as raw material and calcium chloride/formic acid as dissolve system. The mesoporous SiO₂ nanotubes (MSNTs) were obtained with calcining after coating SiO₂ on SF nanofibers templates. Utilizing dynamic covalent bond between aldehyde group (-CHO), which grafting on the wall of MSNTs, and amino group in doxorubicin hydrochloride (DOXHCl), pH-sensitive drug release system was prepared. The microstructure, functionalization of MSNTs and pH-responsive performance of drug loading system were characterized by SEM, TEM, TG, specific surface area (BET) analysis, FTIR and ultraviolet and visible (UV-Vis) spectroscopy. The results show that when SF concentration is 15wt%-17wt%, cylindrical SF fiber templates can be obtained with adjustable diameters ranging from (113±27) nm to (134±32) nm. The wall thickness of MSNTs can be regulated by adjusting the concentration of cetyl trimethyl ammonium bromide (CTAB) in the coating solution. When the concentration of CTAB increases from 1.25 mg/mL to 3.75 mg/mL, the wall thickness of MSNTs increases from 30-39 nm to 63-65 nm, the corresponding specific surface area decreasing from 154 m²/g to 98 m²/g, and the average mesoporous diameter decreasing from 12.5 nm to 10.0 nm. The drug release rate of the MSNTs modified by aldehyde loading with DOXHCl (MSNT-CHO-DOX) reach 23%, 35% and 75% respectively at 100 h when the release is carried out in dipotassium hydrogen phosphate-potassium phosphate monobasic (PB) buffer solution with pH values of 7.4, 6.5 and 5.5, respectively, achieving pH-responsive release of MSNT-CHO-DOX system.