Despite of extensive attention on the ethanol to butadiene (ETB) conversion, the catalyst deactivation during ETB conversion is rarely investigated and poorly understood. Here, the mechanism of the catalyst deactivation during the ETB conversion over Zn-Y/Beta was investigated through several complementary approaches, including XPS, TGA, GC-MS, in situ DRIFTS, UV-vis and C-13 CP MAS NMR spectroscopy. Acetaldehyde was observed to be the first reactive intermediate formed in the ETB conversion, which was rapidly involved in a subsequent aldol condensation with the simultaneous production of acetone. Due to a self- and cross-condensation of acetaldehyde and acetone, long chain unsaturated aldehydes/ketones were formed and further converted to 2,4-dimethyl benzaldehyde via a cyclization reaction, which could gradually cover the active sites and led to catalyst deactivation. Fortunately, the deactivating species could be removed from catalyst surface via simple calcination and the complete regeneration of Zn-Y/Beta could be realized. (C) 2018 Elsevier Inc. All rights reserved.