A novel selective blocking agent called PLA-21 was prepared by acrylamide (AM), Acrylic Acid (AA), diallyldimethylammonium chloride (DMDAAC) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) in aqueous solution with organosilicon(WD-70) as cross-linking agent. The optimal synthesis conditions were discussed detailedly. The experimental results showed that its water plugging rate was higher than 95% and plugging rate of oil was less than 10%, which demonstrated excellent selective plugging ability. Meanwhile, cores with different permeability can be blocked effectively. Compared with some common selective blocking agents, it was found that the PLA-21 satisfied engineering demand better and it was an effective selective blocking agent for oil filed application. FTIR and EDS show PLA-21 was synthesized successfully and it contains anion group, cationic groups, nonionic groups and silicon. SEM was used to research and analyze the mechanism of selective plugging. It indicates that PLA-21 can expand sharply in water and shirk in oil, which making it good selective blocking efficiency.