A side-stream of the cellulose pulping process – tall oil, was valorised for polyol precursor synthesis. The influence of various parameters on the tall oil self-epoxidation method was studied to increase the conversion towards oxirane rings while using a reduced amount of immobilised lipase catalyst – Novozym® 435 and hydrogen peroxide. The influence of synthesis time (0–7 h), process temperature (30–40 ℃), hydrogen peroxide (20–50 wt. %) and Novozym® 435 catalyst concentration (1.5–4.5 wt. % of tall oil mass) on the tall oil fatty acid self-epoxidation process was studied and optimised using response surface method. The shift in relative conversion to oxirane and ethylenic unsaturation was used to track the epoxidation process. The chemical structure change of the epoxidised tall oil was investigated using FTIR, 1H NMR and 13C NMR spectroscopies. The maximum relative conversion to oxirane of 81 % was attained at a relatively high Novozym® 435 catalyst loading of 4.5 wt. %. In comparison, the optimised relative conversion to oxirane of 73 % was achieved at a more feasible catalyst content of 3.2 wt. % after 7 h of synthesis, at hydrogen peroxide and tall oil molar ratios of 2.0/1.0, hydrogen peroxide concentration of 28 wt. % and synthesis temperature of 44 ℃.