Helicobacter　pylori　infections　are　threats　to　public　health　due　to　their　high　infection　rate　and　drug　resistance.　Identification　of　single-nucleotide　variants　(SNVs)　in　H.　pylori　is　crucial　for　both　diagnosis　and　therapy.　Yet　the　clinical　testing　of　resistant　H.　pylori　mutants　is　still　facing　some　challenges,　such　as　the　selectivity　is　not　good　enough　for　SNVs　in　abundant　wild-type　DNA,　the　lack　of　clinical　validation　and　the　economical　burden　on　patients.　Herein,　an　X-shaped　DNA　probe　with　a　toehold　initiator　was　designed,　which　could　specifically　hybridize　with　certain　genotype　DNA　due　to　the　thermodynamically　driven　reaction.　A　competitive　reaction　was　developed　to　amplify　the　thermodynamic　difference　between　wild-type　DNA　and　SNVs,　diminishing　the　interference　of　wild-type　DNA.　By　this　means,　multiple　SNVs　in　H.　pylori　were　successfully　identified　and　two　SNVs　related　to　clarithromycin　resistance　are　chosen　as　model　targets.　A　paper　strip　was　fabricated　for　visual,　fast　screening　of　SNVs.　Furthermore,　the　approach　was　validated　using　clinical　samples,　and　a　point-of-care　(POCT)　testing　diagnosis　was　executed　on　saliva　samples,　demonstrating　its　potential　for　the　prevention　and　cure　of　H.　pylori　infections.　©　2022　Elsevier　B.V.