Objective To study the acute toxicity, genetic toxicity and subchronic toxicity of Tremella polysaccharide and to provide scientific bases for its safe application. Methods Acute oral toxicity, genetic toxicity, and 90 days oral toxicity tests were performed following the national standards of food safety. Results The LD50 of Tremella polysaccharide was more than 12. 0 g/ (kg·bw), and Tremella polysaccharide was a non-toxic substance. The result of the three genotoxicity tests were negative. In the subchronic toxicity test, compared with the negative control group, there were no significant differences (P>0. 05) in bw, weight gain, food intake, food utilization rate, hematological indexes, blood biochemical indexes, urine routine, organ weight, or organ coefficients. Histopathological observations showed no changes related to test factors. The no observed adverse effect level (NOAEL) of Tremella polysaccharide was 7. 21 g/ (kg·bw) for males and 8. 18 g/ (kg·bw) for females. Conclusions No evidence for acute toxicity, genetic toxicity, or subchronic toxicity was observed in this Tremella polysaccharide study.