Abstract: To determine the suitable harvest period of Dendrobium huoshanense, the annual dynamic changes in the physicochemical properties and biological activities of Dendrobium huoshanense polysaccharides was analyzed. The analysis of physicochemical properties using HPGPC, infrared spectroscopy, Ubblelodhe viscometer and spectrophotometry, and the immunoregulatory activity and anti esophageal cancer activity of Dendrobium huoshanense polysaccharide were detected in vitro. The results showed that Dendrobium huoshanense polysaccharides was mainly composed of two fractions with different molecular weights, which consisted of mannose and glucose. Throughout the year, the polysaccharides content and molecular weight of high molecular weight fraction presented a down-up-down-up trend, and its viscosity, acetyl group content and monosaccharide molar ratio showed a down-up-down trend, while the low molecular weight fraction disappeared between May to September. Dendrobium huoshanense polysaccharides had immunoregulatory activity and anti-esophageal cancer activity. The intestinal mucosal immunoregulatory activity of polysaccharides was better from September to April than from May to August, while the inhibitory effect of polysaccharides on the growth of esophageal cancer cells was better in autumn and winter than in spring and summer. By correlating the physicochemical property changes of polysaccharides to their biological activity changes, the suitable period for harvesting Dendrobium huoshanense would be determined to be in the autumn and winter.