Objective：The study aimed to evaluate effects of enteral nutrition on proton pump inhibitors（PPI）-caused adverse gastrointestinal reactions in critically ill patients. Methods：As a cross-sectional study，the study involved all hospitalized patients in the ICUs of 100 hospitals all over the country on April 25th，2017（patients newly admitted on April 25th were excluded）. Self-designed questionnaire items and a standard questionnaire were used. The self-designed questionnaire was composed by patient’s general profile，administered drugs and treatment，nutrition administration，feeding intolerance evaluation and lab test results，while the standardized questionnaire included body mass index（BMI），grade of acute gastrointestinal injury（AGI），sepsis-related organ failure（SOFA）score and acute physiology and chronic health evaluation Ⅱ（APACHEⅡ）score. Single factor analysis was used to investigate whether PPIs could affect gastrointestinal function in patients. Multivariate logistic regression models were performed to investigate whether enteral nutrition has an effect on AGI. Results：①Among the 508 patients who were not given enteral nutrition，a total of 401 patients（78.9%）used PPIs，while the rest 107 patients（21.1%）did not. AGI Grade 4 and Grade 2-3 cases accounted for 3.8% and 17.0% of patients with PPIs treatment，which was significantly higher than that（1.9% and 9.3%，respectively）of non-PPIs groups（P=0.027）. ②Among the 1，138 patients with PPIs administration，724 patients（63.6%）had started enteral nutrition，their AGI score（10.5%，Grade 2-3；0.7%，Grade 4）was superior to the rest 401 cases（35.2%）without enteral nutrition（17.0%，Grade 2-3；3.8%，Grade 4；P < 0.001）. However，the two groups suggested no statistically significant difference in 28-day prognosis. According to the result of multivariable logistic regression，enteral nutrition was an independent protection factor for gastrointestinal function（OR=0.353，95% CI：0.242-0.513，P < 0.001）. Conclusion：Enteral nutrition has an association with protecting ICU patients against PPI-caused adverse reactions of gastrointestinal dysfunction and it does not reduce the death rate.