Abstract Traditional nixtamalization process for producing instant flours is highly time and energy consuming; in addition, it presents problems of high liquid waste discharges (3–10 L H 2O/kg maize). Extrusion represents an alternative technological for producing instant flours and does not generate effluents. The objective of this work was to determine the best combination of extrusion process variables for the production of instant flour from quality protein maize (QPM) ( Zea mays L) V537 variety. Prior to extrusion, the maize kernels were broken to obtain grits (1−2 mm) which were mixed with lime and water to reach a moisture content of 28 g/100 g. The single screw extruder operation conditions were selected from a factorial combination of process variables: extrusion temperature ( ET, 70–100°C), lime concentration ( LC, 0.1–0.3 g/100 g maize) and screw velocity ( SV, 30–80 rpm). A central composite experimental design with five variation levels was chosen. Response surface methodology was applied as optimization technique, over four response variables: in vitro protein digestibility ( PD), total color difference (Δ E), water absorption index ( WAI) and pH. Predictive models for response variables were developed as a function of process variables. The conventional graphical method was applied to obtain maximum PD, WAI, pH and minimum Δ E. Contour plots of each of the response variables were utilized applying superposition surface methodology, to obtain three contour plots for observation and selection of a superior (optimum) combination of ET (79.4°C), LC (0.24 g/100 g maize) and SV (73.5 rpm) to obtain optimized extruded maize flour (EMF) from QPM with a single screw extruder. Optimized EMF had similar physico-chemical and functional characteristics than commercial nixtamalized maize flours (NMF).