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However, the genetic underpinnings of<jats:italic>H. pylori<\/jats:italic>that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative<jats:italic>H. pylori<\/jats:italic>and 24 non-<jats:italic>pylori Helicobacter<\/jats:italic>genomes. There were 1173 conserved protein families of<jats:italic>H. pylori<\/jats:italic>and 673 of all 99<jats:italic>Helicobacter<\/jats:italic>genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the<jats:italic>H. pylori<\/jats:italic>but lacked in non-<jats:italic>pylori Helicobacter<\/jats:italic>species. The operons, genes, and sRNAs within the<jats:italic>H. pylori<\/jats:italic>unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. 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