Tyrosol, a quorum sensing molecule in fungi, significantly improved intracellular protein-polysaccharide (IPS) production by promoting cell growth and stimulating IPS biosynthesis in Trametes versicolor submerged cultures. IPS production was increased to 390 mg/L in tyrosol-induced cultures under optimal concentration (5 mM), which was 1.95-fold higher than that of control cultures. Moreover, IPS from tyrosol-induced cultures (IPS-T) with higher carbohydrate and protein contents mainly contained high molecular weight polysaccharide (97 kDa, 70%), and composed of glucose, mannose and galactose in a molar ratio of 14.8:2.4:1.0. These physicochemical properties led to its stronger antitumor activity. The anti-proliferative mechanism was identified as cell cycle arrest with cell accumulation in S phase and increase in apoptosis. Herein, it is the first report that tyrosol can improve the production of IPS with better antitumor activity. Together these results bring new opportunities in increasing the production and bioactivity of mushroom polysaccharide using microbial quorum sensing molecules. (C) 2017 Elsevier Ltd. All rights reserved.