Objective: To investigate the effects and safety of albumin-bound paclitaxel combined with S-1 in the first-line treatment of advanced gastric cancer. Methods: A retrospective analysis of the clinical data of 58 patients with advanced gastric cancer who received albumin-bound paclitaxel combined with S-1 regimen from April 1, 2018 to April 30, 2020 in the Affiliated Hospital of Xuzhou Medical University was performed. The short-term curative effect was evaluated every two cycles of chemotherapy, the long-term curative effect was evaluated via following up the survival, and adverse reactions were evaluated every cycle according to the NCI-CTC3.0 standard. Results: Among 58 patients with advanced gastric cancer, 4 had complete remission (CR), 32 had partial remission (PR), 13 had stable disease (SD), and 9 had progression disease (PD). The objective response rate (ORR) was 62.1% (36/58), and the disease control rate (DCR) was 84.5% (49/58); the median progression-free survival (mPFS) of all patients was 7.1 months (95%CI: 5.51 to 8.69), and the median overall survival (mOS) was 13.0 months (95%CI: 10.62 to 15.37). Conclusion: The combination of albumin-bound paclitaxel and ticgio regimen in the first-line treatment of advanced gastric cancer is effective, and the adverse reactions are tolerable.