Mushrooms of the genus Hericium spp. represent a series of delicious edible mushrooms with medicinal value. Here, for the first time, the species native to Iran, the mushroom Hericium coralloides , was collected in Mazandaran province, identified, and registered with the NCBI under accession number MW136052. The production of exopolysaccharides (EPS) in submerged culture was optimized using the response surface method. Among the physicochemical and culture medium conditions tested, rotation speed and concentration of maltose and peptone of soybean significantly affected the production of EPS. The proposed model predicts maximum EPS production (0.13 g/L) at 50 g/L maltose, 3 g/L soy peptone, and 1 g/L yeast extract, pH = 6.5, 200 rpm, inoculum at 5% v/v, and 22 °C. The molecular weight of the EPS chains was 413 and 1578 Da. EPS has antioxidant action (EC50 = 6.59 mg/mL) and cytotoxic activity against cancer cells. The viability of AGS and MKN-45 cancer cell lines declined to 20 and 30% after 48 h of the EPS treatment. H. coralloides EPS could be considered a natural dietary anti-cancer supplement. Further studies are necessary to understand the mechanism of the H. coralloides EPS activity on the cell cycle of cancer cells and to prove its action in vivo. Supplementary Information The online version contains supplementary material available at 10.1007/s13399-022-03386-0.