By Auricularia polytricha cultivated by non-genetically modified cotton seed hull as negative control, the toxicological assessment of Auricularia polytricha cultivated by genetically modified cotton seed hull was carried out through acute toxicity test, 90-days feeding test, mice sperm abnormality test, mice bone marrow cell micronucleus test, Ames test and teratogenicity test. As no result of these tests was positive, the safety of Auricularia polytricha cultivated by genetically modified cotton seed hull was preliminarily proved. However, the overall and systematic toxicological assessment should be further studied to determine the feasibility of the genetically modified cotton seed hull using in Auricularia polytricha cultivation.