Background: Neoadjuvant chemotherapies have been widely recommended by clinical guidelines for patients with locally advanced gastric cancer. However, the evidence of combining neoadjuvant chemotherapy with anti-programmed death 1 (anti-PD-1) antibody therapy for patients with locally advanced gastric cancer is inadequate. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of anti-PD-1 antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in patients with locally advanced gastric adenocarcinoma. Methods: Patients with locally advanced(cT3-4 N+ M0, CY0,P0) were enrolled and received four preoperative cycles of XELOX (oxaliplatin 130mg/m², IV, d1 with capecitabine 1000mg/m², bid, d1-d14, q21d) and sintilimab (200mg, IV, q21d). Surgery was performed within 3-4 weeks after completion preoperative therapy. After surgery, patients received four cycles of XELOX. The primary endpoint was the pathological complete response (pCR) rate and the secondary endpoints were major pathologic response (MPR) rate, R0 resection rate, safety, disease-free survival (DFS) and overall survival (OS). This clinical trial is registered at ChiCTR.gov.cn: ChiCTR2000030414. Results: From March 2020 to July 2021, 30 patients were enrolled, with median age 62 years (range30-72), males 18, cT3/T4: 8/22, cN1/2/3: 10/14/6, intestinal diffuse type (Lauren classification):17/13, ECOG PS 0/1/2: 19/8/3. There were 19(63.3%) patients with PD-L1 CPS≥1. All patients were available for preoperative response evaluation, the objective response (ORR) rate was 70.0% (95% CI, 50.6%-85.3%) and the disease control (DCR) rate was 100% (95% CI, 88.4%-100%). All (100%) achieved R0 resection. 10 patients (33.3%) achieved pCR (TRG 0) and 19 patients (63.3%) had MPR (TRG 0-1). Common treatment-related adverse events (TRAEs) were anemia (36.7%), leukopenia (36.7%), neutropenia (30.0%), diarrhea (26.6%), ALT increase (23.3%), AST increase (13.3%), thrombocytopenia (10.0%), vomiting (10.0%). The potential immune-related adverse events (irAEs) were dermatitis (6.7%), hypothyroidism (3.3%), pneumonia (10.0%). Most of the TRAEs and potential irAEs were grade 1 or 2. Grade3 TRAEs and irAEs included ALT increase (3.3%), AST increase (3.3%), dermatitis (3.3%). There were no severe complications and death related to the operation. The median postoperative hospital stay was 8 days (range6-23 days). Conclusions: Sintilimab plus XELOX as neoadjuvant therapy showed an encouraging pCR rate, MPR rate and manageable safety. This combination regimen might provide a new option for patients with locally advanced gastric cancer. Clinical trial information: ChiCTR2000030414.