We investigated the uptake and elimination of cadmium (Cd) and explored the effects of calcium (Ca) on Cd accumulation in Portunus trituberculatus using a two-compartment model. The Cd exposure concentrations were 1 μg/L, 5 μg/L, and 50 μg/L, respectively. We determined the uptake rate constant (k₁), elimination rate constant (k₂), bioconcentration factor (BCF), and biological half-life (B_1/2) using the two-compartment model with non-linear curve fitting. The results showed that the BCF of Cd in hepatopancreas tissue was significantly higher than that in muscle tissue. Both BCF and k1 in hepatopancreas tissues increased with the increase of Cd concentration in water, and the BCF of Cd in hepatopancreas tissue was 12.16, 112.77 and 260.11, respectively. The uptake rate constant (k₁) and elimination rate constant (k₂) in muscle tissue increased with the increase of Cd concentration in water, while the BCF of Cd in muscle tissue from the low to high concentration group was 1.85, 2.45, and 1.97, respectively. The target hazard quotient (THQ) was used to assess the possible health risks to the hepatopancreas and muscle of P. trituberculatus. The results showed that THQs differed in these two tissues; when the exposure concentrations were between 1 μg/L and 50 μg/L, the THQs of Cd in muscles were less than 1; however, the THQs of the hepatopancreas were ＞1 except at 1 μg/L. The results indicated that Cd accumulation in P. trituberculatus muscle posed no significant health risk, but there were serious health risks associated with Cd accumulation in the hepatopancreas unless the Cd exposure concentrations were ＜1 μg/L. In addition, Ca can decrease the accumulation of Cd in the hepatopancreas and muscle of P. trituberculatus, and promote the elimination of Cd from the hepatopancreas. Our findings help to improve the understanding of the control technology and consumption of P. trituberculatus.