In this study, chitosan/polylactide (CP) blend solutions in trifluoroacetic acid as a co-solvent with different blend ratio were electrospun. Effects of different CP ratio and process parameters on the diameter of electrospun nanofibers were experimentally investigated. The fiber morphology and the distribution of fiber diameter were investigated by scanning electron microscopy. Response surface methodology (RSM) was used to define and evaluate a quantitative relationship between electrospinning parameters, average fiber diameters and its distribution for each chitosan-polylactide ratio. Applied voltage and polymer solution extrusion rate are the process variables which control the fiber diameter at similar spinning distances (15 cm). Fiber diameter was correlated to these variables by using a second-order polynomial function. The fibers were of diameter ranging from 94 to 389 nm. The predicted fiber diameters were in good agreement with the experimental results. Contour plots were obtained to identify the processing variables suitable for producing nanofibers. It was concluded that ratio of polylactide and chitosan in the blend polymer played an important role to the diameter of fibers and standard deviation of fiber diameter. The processing factors were found statistically significant in the production of nanofibers.