Objective To investigate the clinical effect of S-1 combined with oxaliplatin (SOX regimen) in treatment of the patients with advanced pancreatic cancer. Methods A total of 106 patients with advanced pancreatic cancer in Qingdao Fuwai Hospital from April 2015 to June 2017 were randomly divided into the treatment group (53 cases) and the control group (53 cases) according to the random number table method. Patients in the control group were treated with S-1 combined with cisplatin treatment, and patients in the treatment group were treated with SOX regimen. The cell proportion of CD3+, CD4+, CD8+and CD4+/CD8+before treatment and after 2 cycles of treatment were detected by using flow cytometry of both groups. The clinical curative effects, immunity and adverse reactions of both groups were compared by usingχ2 test and t test. Kaplan-Meier method was used to make the survival analysis. Results After two cycles of treatment, there were 4 cases of complete remission (CR), 23 cases of partial remission (PR), 17 cases of stable disease (SD), 9 cases of progression disease (PD) in the treatment group, and 0 case of CR, 18 cases of PR, 20 cases of SD, 15 cases of PD in the control group. The rate of CR+PR in the treatment group was higher than that in the control group [50.94％(27/53) vs. 33.96％(18/53)], and there was a statistical difference (χ2=5.936, P<0.05). There was a significant difference in the cell proportion of CD4+and ratio of CD4+/CD8+between the two groups before and after treatment [the treatment group: (27.31±2.48)％ vs. (37.05±2.53)％, χ2= 6.491,P< 0.01; 0.91 ±0.23 vs. 1.53 ±0.50, χ2 = 5.913, P< 0.01; the control group: (27.43 ±2.47)％ vs. (30.32 ± 2.41)％,χ2= 11.214, P<0.01; 0.90±0.22 vs. 1.22±0.34,χ2=7.992, P<0.01]. After 2 cycles of treatment, the cell proportion of CD4+and ratio of CD4+/CD8+of the treatment group were higher than those of the control group, and there were statistical differences (χ2=5.309, P<0.01;χ2= 7.112, P< 0.01). The incidence rate of side effects had no significant difference in both groups after two cycles of treatment [22.64％ (12/53) vs. 18.87％ (10/53), χ2= 1.924, P> 0.05]. The progression-free survival time in the treatment group was longer than that in the control group (P<0.05). Conclusions SOX regimen has a favorable effect on the patients with advanced pancreatic cancer. It can help to improve the immunity and prolong the survival time of the patients.