Abstract: Objective To investigate the effectiveness and safety of SOX regimen combined with D1+ surgery for advanced gastric cancer in elderly patients. Methods Clinical data about elderly gastric cancer patients (≥60 years) admitted to our hospital from January 2013 to December 2015 were retrospectively analyzed. Sixty-four patients who underwent SOX regimen combined with D1+ surgery and 64 patients who underwent D2 surgery were randomly selected in a case-control study. Results The baseline data was well matched in both two groups. The disease control rate and overall response rate of SOX neoadjuvant chemotherapy were 98.44% and 70.31% respectively. Occurrence rates of both grade 3 hematological and non-hematological toxicities were 6.25%, respectively. Compared to D2 surgery, SOX neoadjuvant chemotherapy combined with D1+ surgery had the advantage of shorter operative time (206.72±50.29 min vs 225.81±50.75 min, t=1.913, P=0.034), shorter postoperative ICU stay (21.23±3.56 h vs 33.97±4.43 h, t=3.355, P=0.044), less operative blood loss (241.41±48.99 ml vs 290.63±41.95 ml, t=2.138, P=0.048), and less surgical related complications (9.38% vs 21.88%, χ²=3.793, P=0.048). In addition, the median overall survival was not significantly different between SOX neoadjuvant chemotherapy combined with D1+ surgery group and D2 surgery group in elderly patients with advanced gastric cancer. Conclusion SOX regimen as neoadjuvant chemotherapy combined with D1+ surgery is associated with high efficacy and safety in elderly advanced gastric cancer patients.