The study evaluates the zinc finger homeobox (ZHX) gene family as potential biomarkers for prognosis in lung adenocarcinoma (LUAD), a major histological subtype of lung cancer with high incidence and mortality. Using bioinformatic analysis of online databases and immunohistochemistry, the expression of ZHX family members was investigated. RNA ZHX factors indicated favorable overall survival in lung cancer patients. Subgroup analysis showed associations between ZHX expression levels and survival outcomes in selected patient cohorts. Immunohistochemistry confirmed that low ZHX3 protein expression was strongly correlated with malignant features and adverse overall survival in LUAD patients. Multivariate analysis demonstrated that ZHX3 expression is an independent predictor of prognosis. ZHX3 may serve as a potential biomarker to predict survival in LUAD.