Abstract: The infection and treatment of Helicobacter pylori(Hp) is a hot topic of global concern. However, in recent years, Hp resistance has increased and the eradication rate has decreased in most regions of the world. Therefore, current first-line therapy to eradicate Hp has been adjusted to the quadruple therapy, using more antibiotics and longer duration than the triple therapy. It has an inevitable effect on the gastrointestinal microecology and causes an imbalance of gastrointestinal flora, changes of the composition of the gastrointestinal micro-ecological system, decrease of dominant flora, overgrowth of the intestinal bacteria, and colonization of Clostridium difficile, etc. The above changes are likely related to the adverse reactions during the eradication of Hp and the recurrence of infection thereafter.