Abstract: We investigated the effect of special space environment on cell growth characteristics and malignant phenotype in the Caski human uterine cervix cancer cell line. Caski cell was carried in "Shenzhou Ⅳ" spacecraft and the returning cell was monocoloned. Strains numbered 44F10 was screened out since its increased cell proliferation and tumorigenesis. Moreover, its cell cycle was induced to progress from G1 to S phase, while strains 48A9 were opposite to 44F10 in cytological events. The difference between ground control groups and space groups was significant (P<0.05). Little is known about the underlying changes in gene expression. The purpose of this study was to investigate these changes. Oligonucleotide microarray containing 2 747 probesets was performed on 4410/ control cell and 48A9/ control cell. Total RNA from both cell types was isolated for reversed transcription cDNA probes; hybridization was performed with double pathway-specific gene expression profiling array membrane. Compared with ground control cell, 16 genes were detected to be differentially expressed in group 44F10. There are 36 genes exhibiting differential expression in group 48A9. Among these genes, a high proportion of genes were associated with apoptotic, cell cycle, cell proliferation and cell signal transduction. As expected, several growth-promoting genes were upregulated in group 44F10, while many genes associated with growth restriction were upregulated in group 48A9. The study provides that differential gene expression of uterine cervix cancer cell induced by exposing to the space environment can lead to alteration of phenotype.