The invention relates to human hexahydro uroporphyrinogen III synthetase mutant protein and an application thereof. By using a large number of patients with congenital erythropoietic porphyria and lung cancer as research cases and conducting genetic testing and analysis of the cases, the human hexahydro uroporphyrinogen III synthetase mutant protein is identified, and gene chips, monoclonal antibodies and ELISA (enzyme linked immunosorbent assay) kits are prepared according to the human hexahydro uroporphyrinogen III synthetase mutant protein. The human hexahydro uroporphyrinogen III synthetase mutant protein has the advantages of providing guidance for genetic diagnosis of deficiency and the lung cancer and also providing a theoretical basis for the diagnosis and treatment of related diseases.