In order to explore the process and related genes involved in the accumulation of TTX in the liver and skin of pufferfish, the artificially bred Takifugu flavidus (referred to as "pufferfish") underwent intramuscular injection of 0.25 μg TTX per gram body weight of pufferfish. It was found that the concentration of TTX in the liver was the highest at 4 h after injection (19.12 ng/g), and decreased to 8.92 ng/g at 24 h, TTX was mainly accumulated in hepatocytes; TTX content in the skin was in an upward trend, and it was 13.70 ng/g at 4 h and 22.91 ng/g at 24 h; TTX mainly accumulated in the skin epidermis and basal layer cells. Comparing the control group and the liver and skin transcriptomes 24 h after injection, it was found that: 338 genes were up-regulated and 350 genes were down-regulated in liver tissue by TTX injection, while 598 genes were up-regulated and 595 genes were down-regulated in skin tissue; RT-qPCR verified slc2a12, slc5a7, slc25a22, slc25a15, slc35a3, arap1, ugt2a2, ggt5, psbp2 and other membrane transporter-related genes were significantly up-regulated in the liver and skin after TTX injection (P<0.05), which may be related to the accumulation process of TTX.