Herein, we report the excellent De-NOx performance of La0.7Sr0.3MnO3 (LSM) perovskite-supported Pd catalysts (Pd-LSM) in alternating lean-burn/fuel-rich atmospheres using C3H6 as reductant and describe the in situ activation of the Pd catalysts via metal-support interaction (MSI) tuning. The NOx reduction conversion of the Pd-LSM catalyst increased significantly from 56.1% to 90.1% and the production of N2O was suppressed. Our results demonstrated that this behavior was mainly attributed to the in situ transformation of Pd 2+ into Pd 0 during the reaction. The generated Pd 0 species could readily activate the C3H6 reductant and achieve an eight-fold higher turnover frequency than Pd 2+ for the reduction of NOx. Moreover, excessive MSIs inhibited the in situ generation of Pd 0 , and thereby, lowered the De-NOx activity of the catalyst even at high Pd dispersion. In addition, the Pd-LSM catalysts exhibited much higher S tolerance than conventional Al2O3-supported catalysts.Our study provides a new approach for analyzing and designing highly active metal catalysts operated under dynamic alternating oxidizing/reducing atmospheric conditions.