Background: Advanced gastric cancer has poor prognosis and short survival period. Anti-PD-1 antibodies have shown some efficacy in second-line treatment of advanced or metastatic GC/GEJ cancer, but were not superior to monotherapy. The combination of chemotherapy and anti-PD-1 antibody has been proved to have synergistic effect. Nab-paclitaxel is one of the most commonly used second-line regimens in China. Therefore,we aimed to evaluate the efficacy and safety of sintilimab combined with Nab-paclitaxel in the treatment of advanced GC/GEJ cancer patients. Methods: We retrospectively analyzed patients with advanced GC/GEJ cancer that progressed after first line systemic therapies and treated with sintilimab combined with Nab-paclitaxel from April 1, 2019 to December 31, 2021. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty-nine patients were enrolled and eligible for response assessment. Complete response (CR) was not observed, 15 patients achieved partial response (PR), 16 patients had stable disease (SD) and 9 patients had progression disease (PD). The ORR and DCR were 15 (38.5%) and 31 (79.5%), respectively. Median PFS was 5.4 months (95%CI: 3.072-7.728). We further analyzed PFS between different subgroups of chemoimmunotherapy regimens in order to find which patients could benefit more. Firstly, The PFS of HER2 positive and HER2 negative patients was 7.1months (95%CI:3.367-10.833) and 5.3 months (95%CI:4.018-6.582), respectively (p = 0.947). The median PFS of PD-L1 positive, PD-L1 negative and PD-L1 unknown patients was 5.3months (95%CI:3.744-6.856), 8.1months(95%CI:3.371-12.829) and 6.1 months(95%CI:2.649-9.551)(p = 0.918). Finally, we analyzed the effect of chemoimmunotherapy cycles on PFS. The results showed that PFS of > 4 cycles was numerically longer than that of ≤ 4 cycles, and PFS were 7.1 months (95%CI:4.378-9.822) and 5.2months (95%CI:3.091-7.309)(p = 0.424), respectively. Most of the adverse events (AEs) were grade 1-2.The most common treatment-related adverse events (TRAEs) of grade 3-4 were anemia 5(12.8%), neutropenia 5(12.8%), leukopenia 4(10.3%). The potential immune-related adverse events (irAEs) were grade 1 pneumonia 1(2.6%). Only one patient developed grade 4 hepatitis (2.6%). Conclusions: These results indicated that sintilimab combined with Nab-paclitaxel exhibited good anti-tumor activity and acceptable safety profile as second-line treatment for advanced or metastatic gastric cancer. These results warrant further accrual and evaluation and explore which patients can benefit more from the combined treatment strategy.