The oleaginous yeast Rhodosporidium toruloides has been considered as an economical lipid producer because it transforms carbohydrates from lignocellulosic hydrolyzate into triglycerides; however, R.toruloides cannot survive in hydrolyzate due to the inhibitors co-produced by hydrolysis.We have previously reported a mutant strain M1 8 that had strong tolerance for the stress environments of hydrolyzate were obtained through plasma mutagenesis.Here we applied transcriptomic and proteomic approaches to analyze the global metabolic responses to the stress in hydrolyzate of R.toruloides and elucidate the tolerant mechanism of the mutant strain.The results show that 57% genes matched and correlated well with their corresponding proteins.507 genes and 366 proteins are changed on transcription and expression levels, respectively, and 39 key genes with significantly changed transcription and expression levels (≥5 fold changes) were identified.The results demonstrate that four cellular processes which the key genes are involved in are likely related to the mechanism of tolerance of M18 strain.Enhanced expression of the key genes in R.toruloides could improve the cellular stress tolerance to lignocellulosic hydrolyzate, while the altered expression of most key genes are probably not caused by mutagenesis, but induced by stressful environments of the hydrolyzate.