This study took the advantage of the availability of a methylated mutant (ΔpglX ) of Lacticaseibacillus (L.) paracasei Zhang to test our hypothesis that DNA methylation could protect lactic acid bacteria from freeze-drying and post-freeze-drying storage stresses. Active cultures of the wild-type and mutant were freeze-dried and stored at 30 ℃ for different duration (30, 60, and 90 days) before reactivation. Proteomic analyses was implemented to identify differentially expressed proteins (DEPs) of the bacteria.The confidence of proteomic results was assessed by PRM validation.