The p53 and p21 genes are associated with GI arrest during the cell cycle and with apoptosis, both of which have a close relationship with the effect of chemotherapy. In this study, we investigated the correlation between p53 and p21 expression in biopsy specimens and the histological effect of chemotherapy in esophageal carcinoma. A total of 30 patients with esophageal squamous cell carcinoma received preoperative chemotherapy, then underwent esophagectomy with lymph node dissection. The response rate of primary lesion and metastatic nodes was 20.0% and 25.9%, respectively. The positive rate of p53 and p21 expression was 56.7% and 36.7%, respectively. Preoperative chemotherapy against primary lesions was ineffective in all the patients who expressed p53, but not p21. In contrast, chemotherapy was effective against metastatic lymph nodes which were p53 negative bur p21 positive. These findings suggest that p21 positive expression in the absence of p53 is associated with favorable effects of preoperative chemotherapy in patients with esophageal carcinoma. Therefore, the expression of these genes should be examined in biopsy specimens to predict the chemotherapeutic outcome in patients with esophageal carcinoma.