An amphoteric polymer anti-sloughing agent named WPZY-1 used in air-mist/foam drilling was synthesized using cationic monomer (YD-1), acrylic acid, acrylamide and alkyl substituted acrylamide as raw material, and ammonium persulfate and sodium bisulfate in mass ratio 1:1 as initiator. Its inhibition and anti-sloughing performance was investigated. The optimum dosage of initiator, AA and YD-1 was 0.5%~1.0%, 3%~5% and 5%~10% of total monomers. The performance evaluation results showed that WPZY-1 had strong adsorption capacity and good anti-sloughing property, with a saturated adsorption amount of 100.98 mg/g. The secondary shale recovery rate in 0.5% WPZY-1 solution after 48 hrs was 99.3%. The expansion amount of core after 24 hrs was 1.58 mm. Moreover, the artificial core soaking in WPZY-1 solution could keep regular integrity shape after 10 d with no cracks and peeling phenomenon. WPZY-1 had good compatibility with air-mist/foam drilling agents and its application could effectively improve the inhibition and anti-sloughing performance, and extend wellbore stability time, which met the requirements in high water exit formation.