ABSTRACT: The property differences between bacteria produced from solid-state and liquid-state fermentations have always been the focus of attention. This study analyzed the stress tolerance and transcriptomic differences of the probiotic Lacticaseibacillus casei Zhang produced from solid-state and liquid-state fermentations under no direct stress. The total biomass of L. casei Zhang generated from liquid-state fermentation with MRS medium (LSF-MRS) was 2.24 times as much as that from solid-state fermentation with soybean meal-wheat bran (SSF-SW) medium. Interestingly, NaCl, H2O2, and ethanol stress tolerances and the survival rate after L. casei Zhang agent preparation from SSF-SW fermentation were significantly higher than those from LSF-MRS fermentation. The global transcriptomic analysis revealed that in L. casei Zhang produced from SSF-SW fermentation, carbohydrate transport, gluconeogenesis, inositol phosphate metabolism were promoted, that pentose phosphate pathway was up-regulated to produce more NADPH, that citrate transport and fermentation was extremely significantly promoted to produce pyruvate and ATP, and that pyruvate metabolism was widely up-regulated to form lactate, acetate, ethanol, and succinate from pyruvate and acetyl-CoA, whereas glycolysis was suppressed, and fatty acid biosynthesis was suppressed. Moreover, in response to adverse stresses, some genes encoding aquaporins (GlpF), superoxide dismutase (SOD), nitroreductase, iron homeostasis-related proteins, trehalose operon repressor TreR, alcohol dehydrogenase (ADH), and TetR/AcrR family transcriptional regulators were up-regulated in L. casei Zhang produced from SSF-SW fermentation. Our findings provide novel insight into the differences in growth performance, carbon and lipid metabolisms, and stress tolerance between L. casei Zhang from solid-state and liquid-state fermentations.