Abstract： Objective:To explore the effect of the combination of hyperbaric oxygen（HBO）and gemcitabine（GEM）on the apoptosis of PANC-1 cells and tumor markers in the serum of nude mice with pancreatic cancer.Methods:Fifteen nude mouse models of transplanted tumors of pancreatic cancer were established and randomly divided into control group，GEM group，and HBO+GEM group according to the experimental design，with five mice in each group. The control group was reared normally after successful modeling. The GEM group was treated with 10 mg/kg of GEM by gavage，and the HBO+GEM group was treated with 10 mg/kg of GEM by gavage followed by oxygen inhalation at 0.2 MPa for 60 min. All the three groups were treated every other day for 21 days. The volume and weight of transplanted tumors were measured，the apoptosis of PANC-1 cells was detected by TUNEL staining，and the levels of serum tumor markers were measured using an automated chemiluminescence immunoassay analyzer. The expression levels of apoptosis-related proteins in tumor tissues were measured by western blotting.Results:The tumor volume of the nude mice in the HBO+GEM group was significantly lower than those of the control group and the GEM group on the 6th，9th，10th，15th，18th，and 21st days，with statistically significant differences（ P<0.05）. The tumor weight［（0.54±0.08）g］in the HBO+GEM group was significantly lower than those in the control group［（1.23±0.17）g］and the GEM group［（0.89±0.11）g］，and the differences were statistically significant（ P<0.05）. The apoptosis rate of PANC-1 cells in the HBO+GEM group［（47.26±7.22）%］was significantly higher than those in the control group［（6.83±0.89）%］and the GEM group［（26.84±3.29）%］，and the differences were statistically significant（ P<0.05 or P<0.01）. Compared with the control group and the GEM group，the serum levels of carcinoembryonic antigen（CEA）of the nude mice in the HBO+GEM group were significantly reduced，while the levels of carbohydrate antigen 19-9（CA19-9）and tumor-specific growth factors（TSGF）in the HBO+GEM group were significantly increased，and the differences were statistically significant（ P<0.05）. Compared with the control group and the GEM group，the expression levels of Bax，Caspase-3，and Cytochrome C protein in the transplanted tumor tissues of the nude mice in the HBO+GEM group were significantly higher，while the expression level of Bcl-2 protein was significantly lower，all with statistically significant differences（ P<0.05）. Conclusion:The combination of HBO+GEM can enhance the inhibitory effect of GEM on transplanted tumors of pancreatic cancer in nude mice，and its mechanism may be related to inducing the apoptosis of PANC-1 cells and regulating CEA，CA19-9，and TSGF.