The prognosis for advanced gastric cancer remains very poor due to the limited effectiveness of chemotherapy agents. The range in efficacy of these chemotherapy agents is likely the result of various factors including gene expression. In addition, the emergence of drug resistance during chemotherapy can result in the undesirable outcome of patients experiencing the side effects of chemotherapy without benefiting in terms of tumor response. Gene expression profiling provides a unique opportunity to gain insight into the development of different types of gastric cancer. We applied the TaqMan low density array to investigate the expression of 96 genes in four gastric cancer cell lines (TMK-1, MKN-45, MKN-74 and CDDP-resistant MKN-74). The cell lines displayed different patterns of gene expression alteration after exposure to the chemotherapeutic drugs cisplatin and 5-fluorouracil. We also established that cisplatin-resistant MKN-74 cells do not show the same gene expression patterns as the parental MKN-74 cell line at 0, 8 and 24 h after CDDP exposure. This study reveals the underlying complexity of biological and pathological events and could, perhaps, contribute to new experimental protocols or treatments that would achieve a consistent and desirable outcome of chemotherapy.