In recent years, the instability of atherosclerotic plaques is a hotspot of basic and clinical research. Moreover, it is imperative necessary to accurately identify the vulnerable plaques, and give effectively intervention before acute cardiovascular events. In this work, the stability of atherosclerotic plaques and vulnerable plaques were collected and performed with next-generation of RNA-seq, then data were analyzed. We performed a transcriptome sequence analysis of the vulnerable and stable carotid atherosclerotic plaque by next generation sequencing (NGS) using the Illumina Deep Sequencing technology. We obtained 5,473,799, 3,766,914, 7,713,565 qualified Illumina reads from three vulnerable carotid atherosclerotic plaque, or 5,598,305, 7,249,629, and 5,623,320 qualified Illumina reads from stable carotid atherosclerotic plaque, respectively. Comparative trancriptome analysis differentially revealed 781 genes between vulnerable and stable carotid atherosclerotic plaque, 318 expression of genes was up-regulated and 363 expressions of genes were down-regulated. The volcano plot was used to further identify differential genes expression between the two groups. Cluster analysis was performed, and spearman correlation coefficient was calculated and analyzed. Our work demonstrated differential transcriptomes between vulnerable and stable carotid atherosclerotic plaque. Numbers of genes will serve as a promising resource for revealing the regulatory molecular mechanisms of expression associated with the pathophysiologi and pathogenesis of vulnerable atherosclerosis plaque, even their implications in the field of therapy.