An electrospinning procedure was carried out to fabricate gelatin/poly(epsilon-caprolactone) (Gt/PCL) nanofibers. Response surface methodology based on a three-level, four-variable Box-Behnken design technique was used to model the resultant diameter of the as-spun nanofibers. A second-order model was obtained to describe the relationship between the fiber diameter and the electrospinning parameters, namely Gt concentration, PCL concentration, content of acetic acid in the overall solvent, and content of Gt solution in the blend solution. The individual and the interactive effects of these parameters on the fiber diameter were determined. Validation experiments verified the accuracy of the model which provided a simple and effective method for fabricating nanofibers with a controllable and predictable fiber diameter.