Objective To investigate the changes of high mobility group protein B1 (HMGB1), procollagen type I N-terminal propeptide (PINP) and CD4+ T cells in patients with peptic ulcer and their relationship with Helicobacter pylori (Hp) infection. Methods Our hospital peptic ulcer 97 cases from September 2019 to September 2021 were collected as research objects, which were divide into Hp positive group (n=63) and Hp negative group (n=34) according to whether Hp infection occurs. The 60 cases of physical examination in our hospital from September 2019 to September 2021 were selected as the control group. The levels of serum HMGB1 and PINP were measured by enzyme-linked immunosorbent assay; the CD4+ T cells by flow cytometry. The levels of HMGB1, PINP and CD4+ T cells in peptic ulcer group and control group were compared; The levels of HMGB1, PINP and CD4+ T cells infected with different Hp were compared. Pearson was used to analyze the correlation between Hp infection and HMGB1, PINP and CD4+ T cells; multivariate logistic regression was used to analyze the relationship between HMGB1, PINP, CD4+ T cells and Hp infection.Results The peptic ulcer group levels of HMGB1 were higher than control group, while the levels of PINP and CD4+T cells was lower than control group (P＜0.05). The Hp positive group levels of HMGB1 were higher than Hp negative group, while the levels of PINP and CD4+ T cells was lower than Hp negative group (P＜0.05). Pearson analysis showed that HMGB1 were linearly positively correlated with Hp negative, while PINP and CD4+ T cells were linearly negatively correlated with Hp infection (P＜0.05). Multivariate logistic regression analysis showed that HMGB1, PINP and CD4+ T cells were risk factors for Hp infection.Conclusion The expression of HMGB1 increases in patients with peptic ulcer, while the level of PINP and CD4+ T cells decreases, which is closely related to Hp infection, and is a risk factor for Hp infection