The objectives of this study are to investigate the apoptotic changes in gastric adenocarcinoma following neoadjuvant chemotherapy and to illuminate its correlation with response. One 67 gastric cancer patients with cT2-4 or TanyN1-3M0 between January 2006 and December 2007 were included. All patients had previous gastrectomy and D2 lymphadenectomy with curative intent performed. A total of 12 cycles of preoperative mFOLFOX7 chemotherapy was recommended for all patients, and 83 patients received only adjuvant chemotherapy. Resected specimens were subjected to in situ TUNEL assay and scanned with Applied Imaging Ariol SL-50. Apoptosis index (AI) was significantly higher in the patient received preoperative chemotherapy (CS group) than in the patient did not (S group). In the CS group, AI was found to have a strong positive correlation with the pathological response (rho = 0.403, P = 0.0002). A ROC curve presented a score of 49.4 as the AI cutoff value for response, dividing the CS group into two subgroups with significantly different prognoses (P = 0.003) and further allowing identification of 8 patients with significantly better prognosis out of 48 patients evaluated as grades 1a-b according to a pathological response evaluation (P = 0.022). In conclusion, AI is correlated with efficacy of preoperative chemotherapy and prognosis of gastric cancer patients following neoadjuvant chemotherapy. An AI cutoff value for response may be used as a complementary approach to current pathological response evaluations to help identify potential responders.