Abstract: Objective:To investigate the effect of hyperbaric oxygen(HBO)on enhancing the drug sensitivity of esophageal cancer cell line ECA109 to paclitaxel(Pac)and its mechanism of action.Methods:After the in vitro culture of esophageal cancer ECA109 cells was completed,the cells were divided into four groups according to the experimental design:the control group,the Pac group,the HBO group,and the HBO + Pac group. The control group received Dimethyl sulfoxide;the Pac group received 5 mg/L of Pac(referring to the IC 50 value);the HBO group was exposed to HBO alone for 90 minutes;the HBO + Pac group was exposed to HBO for 90 minutes first and then treated with 5 mg/L of Pac. The proliferation ability of ECA109 cells was detected by the CCK-8 method,the apoptosis of ECA109 cells was detected by flow cytometry,and the expressions of apoptotic proteins,drug resistance-associated proteins,and mitogen-activated protein kinase(MAPK)signaling pathway-associated proteins in ECA109 cells were detected by Western blotting. Results:Compared with the control group and the HBO group,the survival rate of ECA109 cells in the Pac group was significantly decreased,and the apoptosis rate was significantly increased( P<0.05). Compared with the Pac group,the survival rate of ECA109 cells in the HBO + Pac group was significantly decreased,and the apoptosis rate was significantly increased( P<0.05). Compared with the control group and the HBO group,the expressions of proteins(Bcl-2,caspase-9,and ERK)in ECA109 cells of the Pac group and the HBO + Pac group were significantly decreased( P<0.05),and the expressions of proteins(Bad,caspase-3,PARP,p-JNK,and p38)were significantly increased( P<0.05). Compared with the Pac group,the expressions of proteins(Bad and caspase-3)in ECA109 cells of the HBO + Pac group were significantly increased,and the expression of protein P-gp was significantly decreased( P<0.05),while the expressions of proteins(Bcl-2,caspase-9,and PARP)were not significantly changed( P>0.05). Conclusion:HBO combined with Pac treatment can enhance the proliferation inhibitory and apoptosis-inducing effects of Pac on ECA109 cells,and its mechanism of action may be achieved by regulating the MAPK signaling pathway in ECA109 cells.