Annexins (ANXs) are a family of calcium and phospholipid binding proteins that have been implicated in diverse important biological and physiological process. ANX A10 (ANXA10) is a member of this family, though little is known about its functions. In the present study, array based comparative genomic hybridization (CGH) was used to screen DNA copy number change in gastric cancer cell lines and the results obtained were compared with oligonucleotide microarray data. DNA loss of the ANXA10 locus in chromosome 4q33 was found in several gastric cancer cell lines by array based CGH and these cell lines showed decreased ANXA10 expression by oligonucleotide microarray analysis. Functional analysis using siRNA and full-length cDNA transfection in gastric cancer cell lines demonstrated that ANXA10 regulates gastric cancer cell proliferation. Of the 585 primary gastric carcinoma tissues examined, ANXA10 expression at the protein level was found to be reduced in 289 (49.4%) cases. Quantitative real-time PCR analysis validated loss of DNA at the ANXA10 locus in gastric carcinomas with reduced ANXA10 expression. By univariate survival analysis, lack of ANXA10 expression was associated with poor survival (p = 0.016). These results suggest that ANXA10 inactivation by chromosomal deletion may play a role during gastric cancer progression.