Hydrothermal liquefaction (HTL) to biofuel is a promising method for the treatment of animal carcasses, but the commercial viability of large-scale HTL plant needs to be further evaluated. In this study, the model of a HTL plant with the capacity of converting 362 tons pig carcasses to biofuel per day was constructed by Aspen Plus software. Sensitivity and uncertainty analysis were carried out to investigate the key parameters affecting the process economics, based on mass and energy flow data. Results showed the baseline (350°C operating temperature, 30 min residence time, 20 wt% feed solids and 54wt% bio-oil yield) minimum fuel selling price (MFSP) excluding feedstock cost was $ 0.43 per liter gasoline equivalent (LGE). The majority of the MFSP (62.18%) was attributed to the capital cost, while the remaining portion was due to operating cost. The MFSP would be lower than the price of petroleum-based fuel product when the feed flow rate of plant was greater than 48 t day−1. The sensitivity analysis indicated that feed solids loading and bio-oil yield were the most key parameters. A 20% decrease in feed solids loading and bio-oil yield resulted in a 27.34% and 22.91% increase in conversion cost, respectively. The uncertainty analysis took into account the possibility of random variation of residence time, feed solids loading, bio-oil yield, feed flow rate, natural gas/electricity price, heat exchanger coefficient and HTL temperature in actual production. The range of 10% to 90% of MFSP calculated from uncertainty analysis was $0.36~$0.55 LGE−1, with an average value of $0.45 LGE−1. It indicated that the baseline MFSP was less than the actual cost of producing biofuels from hydrothermal liquefaction of pig carcasses.