Objective: To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastrointestinal adenocarcinoma. Methods: 49 patients with pathologically confirmed gastrointestinal adenocarcinoma were randomized into test group (n=25) and control group (n=24). The test group started oral cimetidine intake 400 mg, tid, 7-10d before operation, followed by standard curative operation. The control group did not receive cimetidine. Tumor specimens were paraffin embedded for microsection and stained with hematoxylin and eosin (HE) and Feulgen stain. Morphometric studies and DNA content of tumor nuclei were performed on IBAS Image Analyzer. Results: The tumor cell nuclear area (m m2), nuclear perimeter (m m), maximal nuclear diameter (m m) for test group/control group were 23.54 ± 5.08/34.69± 10.08 (P<0.001), 22.06± 4.43/24.88± 4.05 (P<0.05), 7.84± 1.64/ 8.62± 1.24 (P<0.05), 4.42± 0.61/5.41± 0.89 (P<0.001), Respectively. The percentages (%) of diploidy, triple-tetraploidy, quintuple ploidy, and >quintuple ploidy tumor cells for test group/control group were 16.64± 2.58/5.33± 2.14 (P<0.002), 39.84± 2.28/35.70± 3.58 (P>0.50), 12.42± 5.00/14.48± 0.74 (P>0.20), 31.11± 6.86/ 45.97± 3.82 (P<0.005), respectively. Conclusion: Perioperative administration of cimetidine in gasgtrointestinal cancer patients could decrease the nuclear size and raise the percentage of diploid tumor cells, and convert high aneuploid tumor cells into low-aneuploid tumor cells, which might help reduce the invasiveness of tumor cells.