Pilot tends to have a high prevalence of dyslipidemia. The present study aimed to identify key factors of pilot hyperlipidemia through thorough analysis of physical examination data, and to provide pilot-targeted health guidance to manage hyperlipidemia risks. The physical examination data of 1,253 pilot inpatients from January 2019 to June 2022, were evaluated and divided into two groups based on whether or not the pilot had hyperlipidemia. A total of three multivariate analysis models including logistic model, multilevel model and boosting propensity score were applied to find the risk factors of pilot hyperlipidemia. In the group of pilots with hyperlipidemia, four risk factors, including thrombin time, carbohydrate antigen 199, lymphocyte count and rheumatoid factor, were significantly different from pilots without hyperlipidemia, which might be positively associated with the incidence of hyperlipidemia. In future studies regarding pilots, whether hyperlipidemia is connected to abnormalities in thrombin time, carbohydrate antigen 199 and rheumatoid factor should be further explored. Based on the findings of the present study, pilot health management should be more refined and personalized, and attention should be paid to the risk factors of hyperlipidemia including diet and lifestyle.