This modelling study highlighted the impact of thermodynamic methods on process modelling results and subsequent technical and economic aspects of biofuel production. Fractional distillation of biocrude derived from thermal liquefaction of algae was modelled using three widely used thermodynamic property methods, namely Peng-Robinson, NRTL and PSRK. Process models revealed differences in mass and energy flows when using different thermodynamic models. Most importantly, for different thermodynamic models, significant variations in the separation of key components were found, affecting the proportion of biofuel fractions. One fraction varied in the amount of key components in the range of 100%–600%. These variations subsequently affected financial parameters. The net present value exhibited a difference of between US$7.8 and US$5.8 million when comparing the Peng-Robinson model to the PSRK model in different scenarios, and US$3.4–4.5 million when comparing PSRK and NRTL. The profitability of biofuel production was most dependent on biocrude yield and algae price. A switch-value analysis resulted in an algae feedstock price of $286.20/t, below which biofuel production becomes profitable. By considering two distinct scenarios characterized by different feedstock prices, the minimum fuel selling price was estimated to be competitive with fossil fuels: US$1.1/L when algae was US$474/t and US$0.5/L when algae was cheaper (US$65/t).