OBJECTIVE： To investigate the omeprazole off-label use and provide reference for rational drug use in clinic. METHODS： In retrospective survey， 1 838 omeprazole prescriptions were selected from outpatient department during Jun. 2014 to May 2017 by random number table. According to the latest drug instruction， whether the off-label use or not was determined. Off-label use was determined by reviewing domestic and foreign guidelines， literatures and Micromedex database. RESULTS： Among 1 838 prescriptions， there were 1 750 prescriptions of off-label drug use （95.21％）， involving 13 items and 3 types of off-label drug use. Main type of off-label drug use was over-indication medication， involving 1 747 prescriptions （96.47％）. There was no statistical significance in the incidence of off-label drug use between digestive department and non-digestive department or among physicians at different levels （P＞0.05）. Among 13 items of off-label drug use， 7 items were supported by evidence-based medicine evidence of domestic and foreign guideline， expert consensus/suggestion or literature reports， etc.； among which 1 item of off-label drug use were included in Micromedex grading system and other 6 items had no evidence-based medicine evidence. CONCLUSIONS： The phenomenon of omeprazole off-label use is widespread in outpatient department of the hospital， and some off-label drug use are supported by evidences. There are differences in the quality of those evidences. It is suggested to standardize the off-label drug use to avoid legal risks and guarantee the safety of drug use for patients.