The work aims to study the overall safety of food contact silicone products (FCSPs) by different in vitro cytotoxicity evaluation and test systems to study the difference of different in vitro cytotoxicity test methods. After the samples were simulated in 95% ethanol at 70 ℃ for 2 h, the cytotoxicity evaluation method of FCSPs migration was developed by systematically optimizing the experimental conditions. Four test systems including HeLa-NRU, HeLa-CCK-8, HepG2-NRU and HepG2-CCK-8 were used to evaluate the cytotoxicity of 19 FCSPs marketed in China. The samples showed different cytotoxicity results under different testing systems. Among them, 65% of the samples showed moderate cytotoxicity. The overall biological safety of FCSPs needs urgent attention and in-depth study. This study provides research ideas and scientific basis for the in vitro bioassay of food contact materials.