Abstract: Natural polysaccharides with good biocompatibility and unique tumor immunomodulatory activity are becoming an important adjuvant anticancer therapy in clinic. In the field of pharmaceutics, natural polysaccharides can be used as not only bioactive components but also drug delivery carriers, as well as tumor-targeted ligands.Besides, various novel drug delivery systems based on natural polysaccharides exhibit unique advantages in regulating tumor immune microenvironment. In this review, we summarize the progress on natural polysaccharides in tumor microenvironment(TME) regulation and the designs of nano-sized drug delivery system, and point out challenges of polysaccharide-based drug delivery systems in the future application, and also give the potential solutions for these issues.