Exoskeleton mineralization is a key point in the molting process. Although it has been known that calcium and nutrients change in shrimp and crabs during the period of exoskeleton mineralization, the characteristics of lipid metabolism and its relationship with calcium remain unknown. Therefore, in this study, the Chinese mitten crab was selected as the research object, and 6 experimental crabs were selected in the Premolt stage (D stage) and Postmolt stage (A-B stage) respectively to compare the changes of calcium and nutrients in the different tissues. The metabolic characteristics of nutrients in hepatopancreas were further analyzed by transcriptome analysis. The results showed that the content of calcium in the hepatopancreas and hemolymph was significantly decreased at the postmolt stage (P < 0.05), while the content of calcium in the appendicular muscle was significantly increased at the postmolt stage ( P < 0.05). The ratio of calcium to phosphorus in the hepatopancreas was significantly decreased at the postmolt stage ( P < 0.001), and it showed an opposite trend in appendicular muscle. Triglyceride content in the hepatopancreas was significantly decreased ( P < 0.001), and hepatopancreas triglyceride was significantly correlated with calcium ( P < 0.001). Transcriptome analysis revealed 113 significant differential genes related to lipid metabolism in the hepatopancreas, including 89 up-regulated genes and 24 down-regulated genes. These differential genes were mainly concentrated in steroid hormone synthesis, triglyceride metabolism, fatty acid catabolism, glycerol phospholipid metabolism and linoleic acid metabolism. In conclusion, calcium stored in hepatopancreas are transported to muscle tissue for mineralization of new epidermis during exoskeleton mineralization, and this process is related to hepatopancreas triglyceride. Triglycerides may be broken down to provide the energy or material basis for the exoskeleton mineralization and participate in the synthesis of steroid hormones.