In this study, we analyzed the influence of process parameters on the diameter and orientation of nanofibers electrospun with alternating current (AC), using surface response methodology. The design of experiment was adopted with four main process parameters: solution concentration, collection distance, voltage and collection speed. The morphology of nanofibers was examined with a scanning electron microscope. Nanofiber orientation was characterized by the fast Fourier transform method. We used the Box-Behnken design model to predict the diameter and orientation of the nanofibers, and the results showed good agreement with the measured results. The results also indicated that solution concentration and collection speed have a similar influence on fiber diameter and orientation, as in the case of direct current electrospinning. Furthermore, in this study, we optimized the process parameters to generate thinner nanofibers with better alignment, and it also can be used as a reference to make nanofiber yarns with AC electrospinning. Display omitted •We studied the parameter effects on the AC electrospun nanofiber diameter and orientation with response surface methodology.•We used the Box-Behnken design model to predict the nanofiber diameter and orientation.•Concentration and collection speed had similar influences on fiber diameter and orientation in AC and DC electrospinning.