Vanadium catalyst supported on nano-HZSM-5 was utilized in oxidative dehydrogenation of propane to propylene. The physicochemical properties of the elaborated catalysts were investigated by means of XRD, SEM, FTIR spectra, UV-vis, Raman, NH3-TPD and H-2-TPR techniques. The effect of vanadium loading (2-10 wt %), temperature (500-600A degrees C) and oxygen to propane ratio (0.5-1.5) on conversion, propylene and ethylene selectivity was studied using full factorial design of experiments. The obtained data were statistically analyzed using the Analysis of Variance (ANOVA) and a p < 0.05 was considered statistically significant. The mathematical relationship of conversion, propylene and ethylene selectivity on three independent variables approximated by a second-order quadratic model. Two-dimensional contour plots were drawn to investigate the effect of independent variables and their interaction on the chosen responses. The function of temperature, oxygen to propane ratio and vanadium content such as acidity and reducibility on the performance of supported vanadium catalysts were discussed.