Abstract: OBJECTIVE To study the effect of 5-FU thermochemotherapy on the proliferation of BGC-823 cells by response surface methodology. METHODS The logarithmic growth of BGC-823 cells was used to investigate the effects of 5-FU on the inhibition rate of BGC-823 cells, including:incubation time, incubation temperature and drug concentration. Design-export 8.5 was used to integrate the values of each index, and a three-dimensional response surface graph was constructed to analyze the interaction. The optimal thermochemotherapy conditions were optimized, and the optimized experiment conditions were verified. RESULTS After integrated analysis, it was found that the concentration, incubation time and incubation temperature all had effects on the proliferation of BGC-823 cells. The order of effects was drug concentration > incubation time > incubation temperature. In addition, the interaction between incubation time and incubation temperature was also significant. The optimized thermochemotherapy conditions were:16 000 μg·mL^-1 of drug concentration, 20 min of incubation time, 40℃ of incubation temperature. After three validation tests, it was confirmed that the cell inhibition rate could reach 43.18%, which was only 0.85% deviation from the predicted value of the model. CONCLUSION Thermotherapy can enhance the inhibitory effect of 5-FU on BGC-823 cells.