Edible mushrooms possess dual potential of high nutritional value and bioactivity, being gaining popularity. They are particularly susceptible to enrichment with heavy metals, especially cadmium (Cd), limiting the edible safety and commercial value of edible mushroom. Therefore, it is particularly important to extract Cd as much as possible to achieve rapid monitoring of the heavy metal Cd in mushroom. However, the common Cd extraction process possesses challenges such as long time-consuming, high cost, and environmental pollution. Herein, the study developed a microwave-enzyme assisted extraction for Cd using response surface methodology, which exhibited the advantages of being green and efficient. Compared with the national standard method (pressure digestion tank digestion method) in China, this method significantly increased the Cd content in the fruiting body of Agaricus subrufescens, Agrocybe aegerita, Flammulina velutipes, Coprinus comatus, Hohenbuehelia serotina, Pleurotus eryngii, Cordyceps Militaris, Lentinus edodes, Grifola frundosa, and Morchella esculenta, especially the Cd extraction of Coprinus comatus and Hohenbuehelia serotina increased by 166.150 % and 173.280%, respectively. The study demonstrates the applicability of the present microwave-enzyme assisted approach for the extraction of Cd from mushroom.