Abstract： Objective:To investigate the sensitization effect and mechanism of hyperbaric oxygen（HBO）assisted hypofractionated radiation（HFRT）in treating mice with non-small cell lung cancer（NSCLC），monitored by the PET/CT with fluorine-18 fluoroerythronitroimidazole（18F-FETNIM）as the marker.Methods:The transplanted NSCLC tumor model was established in nude mice which were randomly divided into three groups：HFRT group（ n=40），HBO-assisted HFRT group（ n=40），and hypoxia-assisted HFRT group（ n=40）. In the HFRT group，the tumors on the left hind limbs of tumor-bearing mice were exposed to a high-dose-per-pulse of 6 MeV electron beam，with 1 m source-to-surface distance under 20 Gy. On the basis of the treatment in the HFRT group，the hypoxia-assisted HFRT group was given 10.0% hypoxic mixed gas at 5 L/min；while the HBO-assisted HFRT group was given HBO therapy. The PET/CT was used to dynamically evaluate the metabolic changes of 18F-FETNIM，and the maximum standardized uptake value（SUVmax）of the tumors was obtained. The expression levels of Ki-67 and hypoxia inducible factor-1α（HIF-1α）in tumor tissues of the three groups were detected by immunohistochemistry，and their correlations with SUVmax were analyzed. Results:Compared with the HFRT group and hypoxia-assisted HFRT group，the radioactive SUVmax，the proportion of Ki-67 positive cells，and the number of HIF-1α positive cells shown in the semi-quantitative analysis of the tumor-bearing mice in the HBO-assisted HFRT group decreased significantly，and all the differences were statistically significant（ P<0.05 or P<0.01）. Pearson test showed that the SUVmax was positively correlated with the expressions of Ki-67 and HIF-1α（ r=0.677， P<0.01； r=0.445， P<0.05）. Conclusion:The PET-CT with 18F-FETNIM imaging shows that HBO can enhance the radiosensitivity of HFRT treatment on NSCLC transplanted tumor tissues in nude mice，and its mechanism might be related to the inhibition of Ki-67 and HIF-1α expressions.