The lithium-sulfur battery is one of the most promising battery technologies with high energy density that exceeds the presently commercialized ones. The shuttle effect caused by the migration of soluble polysulfides to the lithium anode is known as one of the crucial issues that prevent the Li-S batteries from practical application. Modification of the separator is regarded as a convenient yet efficient strategy to alleviate the shuttle effect. In this report, we use a thermally stable and chemically robust metal-organic framework (MOF), UiO-66, as a physical and chemical barrier for soluble polysulfides to functionalize the commercial polypropylene separator. The Li-S cell assembled with such a separator shows a significantly improved cycling stability with an average specific capacity of ca. 720 mA h g-1 at a current rate of 0.5 C for 500 cycles. Experimental and theoretical investigations indicate that the cell performance enhancement results from the physical restriction of the MOF barrier layer and strong chemical interaction between UiO-66 and polysulfides. The excellent thermal stability and chemical robustness (in acid/alkali solutions, conventional organic solvents, and polysulfide electrolytes) of UiO-66 make it highly competitive among various materials developed for separator modification in Li-S batteries.