Abstract: OBJECTIVE To investigate the level and clinical significance of CD₄⁺Chemokine C-X3-C-motif receptor 1(CX₃CR₁)⁺T lymphocytes in the peripheral blood of patients infected with Helicobacter pylori (Hp). METHODS A total of 51 patients infected with Hp admitted to the Health Medicine Department of the Second Medical Center of Chinese PLA General Hospital from Dec. 2024 to Jun. 2025 were selected as the infection group, and 50 individuals with negative Hp undergoing physical examinations during the same period were selected as the control group. General clinical data were compared between the two groups. The proportion of CD₄⁺CX₃CR₁⁺T lymphocytes in CD₄⁺ T cells in peripheral blood and its relationship with different types of Hp infection were detected and analyzed. The differences in white blood cell count (WBC), neutrophil proportion, lymphocyte proportion, monocyte proportion, eosinophil proportion and basophil proportion between the groups were detected and compared. The diagnostic value of the proportion of CD₄⁺CX₃CR₁⁺T lymphocytes for Hp infection was analyzed based on the receiver operating characteristic (ROC) curve. RESULTS The proportion of CD₄⁺CX₃CR₁⁺T lymphocytes in CD₄⁺ T cells was 3.65 (2.31, 5.48) in the Hp infection group and 8.47 (3.86, 11.48) in the control group, with a statistically significant difference (P＜ 0.001). There was no statistically significant difference in the proportion of CD₄⁺CX₃CR₁⁺T lymphocytes in CD₄⁺ T cells in peripheral blood between type I and type II Hp infections (P= 0.441). ROC curve analysis showed that the area under the curve for predicting Hp infection based on the proportion of CD₄⁺CX₃CR₁⁺T lymphocytes was 0.753. CONCLUSION The proportion of CD₄⁺CX₃CR₁⁺T cells in CD₄⁺ T cells in peripheral blood significantly decreases in patients infected with Hp, which holds important diagnostic value for Hp infection.