Abstract: Objective To investigate the factors influencing compliance with standard quadruple therapy in patients with Helicobacter pylori (Hp) infection, and to provide a basis for formulating scientific pharmaceutical intervention strategies. Methods A total of 174 patients with Hp infection admitted to The People’s Hospital of Rugao of Nantong City from June 2021 to June 2024 were enrolled. Their compliance with standard quadruple therapy was evaluated using a unified standard, and the patients were divided into a good compliance group and a poor compliance group. The clinical baseline data of the two groups were compared, and Logistic multivariate regression analysis was used to screen and summarize the key factors affecting treatment compliance. Based on the identified influencing factors and evidence-based medical evidence, the pharmaceutical intervention strategies to improve patients, compliance with standard quadruple therapy were discussed. Results The overall compliance rate of 174 patients with Hp infection to standard quadruple therapy was 55.17%. The Hp eradication rate was significantly higher in the good compliance group (84.38%) than in the poor compliance group (69.23%), the difference was statistically significant (P ＜ 0.05). Logistic multivariate regression analysis showed that manual labor, lack of medical insurance, and lack of knowledge about Hp infection were independent risk factors affecting patients’ compliance with standard quadruple therapy (P ＜ 0.05); age ＞ 40 years and education level of senior high school or above were protective factors (P ＜ 0.05). Conclusion The overall compliance of patients with Hp infection to standard quadruple therapy is relatively low, and low compliance is directly associated with the decrease in Hp eradication rate. Clinically, it is necessary to strengthen health education for key populations such as manual workers, patients without medical insurance, and those with insufficient Hp knowledge, and implement individualized pharmaceutical interventions to improve treatment compliance and Hp eradication effect.