In this study, surface roughness generated by face milling of 38CrSi high-strength steel is discussed. Experiments based on 24 factorial design and Box-Behnken design method are conducted to investigate the effects of milling parameters (cutting speed, axial depth of cut and radial depth of cut and feed rate) on surface roughness, and a second-order model of surface roughness is established by using surface response methodology (RSM); Significance tests of the model are carried out by the analysis of variance (ANOVA). The results show that the most important cutting parameter is feed rate, followed by radial depth of cut, cutting speed and axial depth of cut. Moreover, it is verified that the predictive model possesses highly significance by the variance examination at a level of confidence of 99%. And the relationship between surface roughness and the important interaction terms is nonlinear.