Objective To systematically analyze the current status of clinical tube feeding medication administration, the differences in knowledge-attitude-practice (KAP) among medical and nursing staff, and the associated influencing factors. Methods A combined approach of retrospective analysis and preliminary questionnaire survey was adopted. Medical records of inpatients receiving tube feeding medication in The First Affiliated Hospital of Naval Medical University from Jul. to Dec. 2024 were retrieved, and the inappropriate medication orders were statistically analyzed. Based on the KAP theoretical framework, a KAP questionnaire on tube feeding medication for physicians and an operation questionnaire for nursing staff were separately developed. A single-center small-sample exploratory survey was conducted to evaluate the cognitive level, attitudinal orientation and practical behavioral characteristics of staff in different positions regarding tube feeding medication administration. Results A total of 12 934 medication orders were included, involving 297 types of drugs. The top 5 departments with the highest frequency of tube feeding medication administration, namely the emergency department, geriatrics department, gastroenterology department, thoracic surgery department, and respiratory department, accounted cumulatively for 78.86% (10 200/12 934). The irrational medication orders for tube feeding medication were primarily manifested as improper use of special dosage forms (57.52%, 325/565), mainly involving enteric-coated tablets and sustained/controlled-release tablets. In addition, 12.59% (1 629/12 934) of the orders involved injectable preparations administered via feeding tubes, of which hypertonic sodium chloride solution and others posed potential safety risks via this route. The questionnaire survey revealed that the physicians generally exhibited favorable KAP toward tube feeding medication administration, yet 64.71% (11/17) had cognitive gaps concerning the suitability of specific drugs such as aspirin enteric-coated tablets. Non-standard practices were prevalent among the nursing staff; nursing assistants showed significantly lower compliance than registered nurses in tube flushing methods, drug mixing and grinding, and adherence to standard procedures (all P＜0.01). Over 80% of both physicians and nurses reported demands for professional training and pharmaceutical quick-reference tools. Conclusion Clinical tube feeding medication administration is plagued by issues including improper use of special dosage forms and unsuitable administration routes. Physicians have insufficient knowledge on specific drugs, and the operational standardization of registered nurses and nursing assistants requires improvement. Current management and training support fail to fully meet clinical requirements. It is recommended to formulate standardized guidelines, optimize the electronic medical order system, strengthen multidisciplinary collaboration, and implement targeted training, so as to improve the rationality and safety of tube feeding medication administration.