Natural sepiolite was treated with HCl solution to change its surface and internal structure and the structure of sepiolite was cracked to produce SiO2 when the concentration of HCl is more than 2 mol/L. The Mo-Bi-Fe-Co-V-Sb-O/sepiolite catalyst was prepared through impregnation — precipitation method and characterized by means of X-ray diffraction, scanning electron microscopy and energy dispersive spectrum techniques. The effects of temperature, volume fractions of NH3 and O2, and space velocity of feed gas on catalytic activity were evaluated in a fixed bed reactor. The results show that propane conversion of 82% and selectivity to acrylonitrile of 38% can be obtained at 490 °C, V(C3H8) : V(NH3) : V(O2)=1.00 : 1.05 : 2.50 and space velocity of 3000 cm3 · g−1 · h−1.