The influence of pulping variables on the pulp and black liquor properties for a neutral sulphite semi-chemical pulping system was investigated in a pilot plant pulping setup situated at an industrial paper mill. Eucalyptus chips were used as raw material and the operating variables were Na2SO3 charge (8–18% w/w on oven-dry wood), Na2CO3 charge (0.5–3.0% w/w on oven-dry wood) and maximum cooking temperature (160–180 °C). Response surface methodology was used to parametrize empirical models to find the optimal conditions for maximizing the short-span compression strength index of the pulp. The derived regression models for the black liquor properties and the pulp hypo number had R2-adjusted values above 0.8 and p-values for overall significance below 0.05. The derived regression models for the handsheet strength properties had R2-adjusted values between 0.3 and 0.45 and p-values for overall significance either below 0.05 or between 0.05 and 0.1. The sulphite charge, followed by the carbonate charge, had the most notable effect on the evaluated properties with the effects of temperature being less significant. Optimization of the pilot plant system showed that the short-span compression strength index of the pulp could be maximized to 26.7 N m/g, using a sulphite charge of 9.4% (w/w on oven-dry wood) and a carbonate charge of 1.94% (w/w on oven-dry wood), similar to short-span compression strength indices typically achieved using other pulping processes.