Recently, a dengue virus-induced apoptosis p53-and mitochondria-mediated were reported in human and animal cells. To understand further the underlying mechanisms, a p53-deficient cell line, H1299, and a p53-knockin cell line, H273, were infected with dengue type 1 virus and the cellular gene expression profiles at the mRNA level were analyzed by affymetrix array analysis. The results showed 183 genes with at least twofold increase at mRNA expression level in dengue virus-infected cells. Among the 183 genes, 68 genes were up-regulated in both H1299 and H273 cells and 78 genes were found to be up-regulated in only H273 cells. Eleven selected genes, mainly involved in IFN-pathway, cell cycle, signal transduction, and ubiquitin-proteasome pathways were confirmed using qualitative and quantitative PCR. Interestingly, an approximately 32-fold increase in caspase-1 expression was observed in the p53-knockin cell line, H273. Gene silencing of caspase-1 or inhibition of caspase-1 activity led to reduction in dengue virus-induced apoptosis with minimal effect on virus replication.