Cancer is one of the communal reasons -for death worldwide. Periplaneta americana (P. americana) hemolymph revealed a wide range of biological activities, including antibacterial, anticancer, antiviral, and antiinflammation. Using histopathological approaches, this study was conducted to evaluate the safety of P. americana hemolymph by investigating its toxicological effects on liver, kidney, and spleen tissues of Solid Ehrlich carcinoma cells bearing mice. The results showed remarkable inflammatory and necrotizing toxic effects of P. americana hemolymph on mice's liver with no remnant of liver tissues. It also induced tubular necrosis of renal tubular kidney tissue, and lymphoid hyperplasia with significant congested red pulp in spleen tissue after treatment for 14 days. These findings concluded that P. americana hemolymph has prominent hepato-renal and splenic cytotoxic effects of Solid Ehrlich carcinoma cells bearing mice. The histopathological data of P. americana hemolymph should be considered while using these materials in the discovery and development of anticancer agents.