Anticancer drugs resistance is often ascribed to gene mutation,amplification or epigenetic changes that affect the uptake,metabolism or export of drugs at the cell level.Tumor physical microenvironment not only influences the drug distribution but also causes difference in cell proliferation rate and hypoxia or acidosis due to its heterogeneity,which could affect the tumor drug resistance.This review discusses the relationship between cancer physical microenvironment and drug resistance and the strategies for enhancement of the chemotherapy sensitivity through modification of the tumor physical microenvironments,as well as foreground of the research.