Hemocyanin (HCY) is a multifunctional glycoprotein, which plays multiple roles in immune defense in invertebrates. HCY from some mollusks can induce potent immune response, while little is currently known about how hemocyanin from arthropods affects tumors. In the present study, in vitro cytotoxic effect of HCY from two crab species Atergatis roseus and Eriphia verrucosa was investigated on two cell lines included hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). The results showed that HCY exhibited degrees of inhibitory activity against the two cell lines. HCY of A.roseus showed the highest cytotoxicity against HepG-2 cell line(IC₅₀ :7.7 ± 3.1 mg/ml) while the HCY of E.verucossa  showed inhibitory effect  (IC₅₀ : 9.5 ± 2.6 mg/ml) after 72 h. HCY of A.roseus  and E.verucossa showed their maximum cytotoxity IC₅₀ towards MCF-7 at 2.71± 1.3 mg/ml and 4.72± 1.5 mg/ml, respectively. In Conclusion, We concluded that HCY obtained from A. roseus has strong anti-tumor activity against HepG-2 and MCF-7 than HCY obtained from E. verrucosa