In this study, the tissue staining differences between thorn and bud of sea buckthorn were compared by tissue section analysis, the gene expression profile differences between thorn and bud were compared by transcriptome sequence analysis, and the expression level of candidate genes was verified through qRTPCR, for providing candidate genes for further regulating the development of sea buckthorn by genetic engineering. The results showed that: (1) the tissue boundary of the transverse section of the sea buckthorn bud was obvious and hierarchical, while the tissue boundary of the transverse section of the sea buckthorn was blurred, the type of staining area was monotonous, the red area in the center of the thorn tip was larger and the spontaneous fluorescence of lignin indicated a significant increase in the lignification degree of the thorn. (2) 81 560 unigenes were assembled by transcriptome analysis, including 9 385 differentially expressed genes (DEGs). (3) GO and KEGG enrichment analysis showed that the most enriched genes were mainly related to the development of cell wall, epidermis and stomata, especially the lignin synthesis pathway. The analysis of bud and thorn related DEGs showed that there were 20 DEGs related to lignin synthesis, a total of 29 DEGs related to cutin, suberine and wax biosynthesis, a total of 14 DEGs related to plant epidermal development and stomatal complex development. It was speculated that some HOTHEAD protein genes were involved in controlling the disappearance of apical meristem of sea buckthorn, and lignin synthesis related genes were closely related to the process of thorn hardening based on literature analysis. (4) qRTPCR analysis showed that three of the six selected lignin synthesis related DEGs were upregulated by 9.5, 41.1 and 13.7 times, while the other three were down regulated by 5%, 14% and 24%, respectively; Among the four selected cutin, suberine and wax biosynthesis related DEGs, two were upregulated by 3.6 and 22.1 times, and the other two were down regulated by 3% and 6%, respectively; The four selected epidermal and stomatal development related DEGs were down regulated to 6%, 13%, 3% and 4%; The relative expression level of key genes can be mutually confirmed with the TPM value measured by transcriptome, indicating that the verification results were consistent with the transcriptome analysis results. Overall, this study provided insight that there were significant morphological and histological differences between thorn and bud of sea buckthorn, and the DEGs between them were mainly related to lignin synthesis and the development of cell wall, epidermis and stomata.