Objective To investigate the correlations of the blood flow grade of lung adenocarcinoma on ultrasound with microvascular density (MVD) and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in tumor tissue as well as clinical stage and its significance. Methods A retrospective analysis was performed on the clinical data of 108 patients with lung adenocarcinoma. The patients were divided into blood flow level 0 (group A), blood flow level Ⅰ (group B), blood flow level Ⅱ (group C), and blood flow level Ⅲ (group D) based on the blood flow level of tumor tissue on ultrasound. The four groups were compared for MVD values and positive expression of VEGF and HIF-1α in the tumor tissue; meanwhile, analyses were performed for the correlations of the blood flow grade of lung adenocarcinoma on ultrasound with MVD and expression of VEGF and HIF-1 α in the tumor tissue as well as clinical stage. Results There were significant differences in MVD and positive expression rates of VEGF and HIF-1α in the tumor tissue between the groups (F=116.487,χ2=7.143,6.982,P<0.05), with significantly higher MVD values in groups B, C, and D than in group A, significantly higher MVD values in groups C and D than in group B, and significantly higher MVD values in group D than in group C (P<0.05), and with significantly higher positive expression rates of VEGF and HIF-1α in groups C and D than in group A and significantly higher positive expression rates of VEGF and HIF-1α in group D than in groups B and C (χ2=4.589-112.502,P<0.05). There were positive correlations of blood flow grade with MVD and positive expression rates of VEGF and HIF-1α in the tumor tissue as well as clinical stage (r=0.705-0.836,P<0.05). Conclusion There are correlations of the blood flow grade of lung adenocarcinoma on ultrasound with MVD and expression of VEGF and HIF-1α in the tumor tissue as well as clinical stage. This is useful in evaluation of early-stage tumors and preoperative conditions.