<p>Lung recurrence following hepatectomy is a common and clinically significant complication in patients with hepatocellular carcinoma (HCC), often leading to poor prognosis. However, the underlying mechanisms and reliable predictive biomarkers remain poorly defined. We performed cDNA microarray analysis to identify genes associated with lung recurrence after hepatectomy in HCC patients and identified lysyl oxidase (LOX) as a candidate. We further evaluated the association between LOX expression, circulating tumor cell (CTC), and microvessel density (MVD). The predictive value of serum LOX levels was assessed in both training and validation cohorts. LOX expression was significantly elevated in HCC patients who developed lung recurrence post-hepatectomy and was associated with worse prognosis. High intratumoral LOX expression correlated with increased CTC counts and elevated MVD. In vitro, LOX overexpression enhanced HCC cell migration and invasion, while LOX knockdown suppressed these phenotypes. Serum LOX levels demonstrated predictive potential for postoperative lung recurrence in both cohorts. LOX overexpression is closely associated with lung recurrence after hepatectomy in HCC patients. LOX may serve as a potential biomarker, and its serum level could be used to predict postoperative lung recurrence.</p>