Furan, a Group 2B carcinogen, is often found in heat-processed foods and has several precursors including ascorbic acid, carbohydrates, amino acids, polyunsaturated fatty acids, and carotenoids. It is particularly harmful when present in baby food. To determine the factors contributing to formation of furan in food, four types of lactose-amino acid models were constructed based on the composition and content of free carbohydrates and amino acids in mashed tuna. A two-level, fractional factorial experiment was designed to systemically investigate the effects of sterilization time, sterilization temperature, pH, phase state, and buffer system on the furan formation. The results showed that the effects of these factors were similar in all four lactose-amino acid models, wherein, high temperature, long durations of sterilization, neutral pH, liquid state, and the presence of phosphates all promoted the furan formation. Additionally, phase state had a relatively lesser impact as compared to the other factors tested. This work provide data for the prevention and control of furan formation in food as well as a reference for the study of other hazards in food.