Objectives: Limited information is available about the biological characterization of peri-implant soft tissue at the transcriptional level. The aim of this study was to investigate the effect of dental implant on the gingival tissue in vivo by using paired samples and compare the differences between peri-implant and periodontal gingiva at the transcriptional level.Methods: Paired peri-implant soft tissue and periodontal gingiva tissue from 6 patients were obtained, and the pooled RNAs were analyzed by deep sequencing. Venn diagram was used to further screen out differentially expressed genes in every pair of samples. Annotation and enrichment analysis was performed. Further veri cation was done by quantitative real-time PCR.Results: A total of 3549 genes including were found differently expressed between peri-implant and periodontal groups. The Venn diagram further identi ed 185 genes differentially expressed genes (DEGs) in every pair of samples, of which the enrichment analysis identi ed signi cant enrichment for cellular component was associated with external side of plasma membrane, for molecular function was protein binding, for biological process was immune system process, and for KEGG pathway was cytokinecytokine receptor interaction. Among the DEGs, CST1, SPP1, AQP9 and SFRP2 were veri ed to be upregulated in peri-implant soft tissue.Conclusions: Peri-implant gingiva showed altered expressions of several genes related to the cell-ECM interaction.Clinical Relevance: At the transcriptional level, healthy periodontal is alternative to the healthy periimplant soft tissue as the control of peri-implantitis to a large extent, except in the research related to cell-ECM interactions.