Background This study evaluated the prognostic impact of D2 lymphadenectomy combined with splenectomy in patients with advanced proximal gastric cancer and lymph node metastasis at the splenic hilum (No. 10 lymph nodes).Methods The clinical records of 216 patients with advanced proximal gastric cancer and No.10 lymph node metastasis who underwent D2 curative resection were retrospectively analyzed. Seventy-three patients underwent simultaneous splenectomy (splenectomy group), while 143 patients did not (spleen-preserving group). Five-year survival rates, mean numbers of dissected No.10 lymph nodes and metastatic No.10 lymph nodes, and operative morbidity and mortality were calculated and compared between the two groups. Potential prognostic factors were evaluated by univariate and multivariate analysis.Results The 5-year survival rate was 30.0% for the splenectomy group and 19.7% for the spleen-preserving group (X~2=14.73, P <0.05). The mean numbers of dissected No.10 lymph nodes and metastatic No.10 lymph nodes in the splenectomy group were significantly greater than in the spleen-preserving group (P <0.05). Multivariate analysis revealed that the depth of invasion, splenectomy, and type of gastrectomy were independent prognostic factors. The survival rate for T3 patients with and without splenectomy was 38.7% and 18.9%, respectively (X~2 =15.03, P <0.05). For patients undergoing total gastrectomy, survival rates were 33.4% and 20.7%, respectively (X~2=13.63, P<0.05). Operative morbidity and mortality in splenectomy group was 24.7% and 4.1%, respectively, and in the spleen-preserving group was 17.5% and 3.5%, respectively. The differences were not statistically significant (P >0.05).Conclusions Splenectomy is beneficial for No.10 lymph node dissection in patients with advanced proximal gastric cancer. To improve patient prognosis, total gastrectomy with splenectomy is recommended for patients with T3 proximal gastric cancer who have No. 10 lymph node metastasis.