Abstract: 【Objective】The member identification，phylogenetic analysis and stress response analysis of watermelon OSCA gene family were carried out to provide reference for revealing the biological function and molecular mechanism of stress resistance of watermelon OSCA gene.【Method】The members of watermelon OSCA gene family were identified by bioinformatics method from watermelon genome database，and named according to chromosome location information. Chromosome position，gene structure，collinearity，promoter，protein structure and phylogeny of gene family members were analyzed comprehensively. Transcriptome data and qRT-PCR were used to analyze OSCA gene expression in watermelon under stress.【Result】Watermelon OSCA gene family had 10 members，which were unevenly distributed on 6 chromosomes. The molecular weight of watermelon OSCA protein varied from 24.59 to 91.97 kD，and the number of amino acids ranged from 214 to 809 aa，most of which were located in the plasma membrane. The results of collinearity analysis showed that the fragment replication event occurred during the evolution of watermelon OSCA gene. The watermelon OSCA gene family was divided into three groups，and the exon-intron composition pattern，conserved motif arrangement of protein，the number proportion of secondary structure and the tertiary structure model of the members of the same group were similar. The OSCA genes of watermelon，rice，tomato and Arabidopsis thaliana were divided into 6 subgroups，watermelon OSCA gene was distributed in each subgroup. The promoter region of OSCA gene in watermelon contained several abiotic stress response elements such as anaerobic induction，cold stress response，light response and drought stress response. Under drought，low temperature and salt stress，the expression levels of OSCA gene family members in watermelon all changed to different degrees，and the expression levels of ClaOSCA3 and ClaOSCA5 all changed significantly under three different stress conditions（P<0.05）.【Conclusion】Watermelon OSCA gene is conserved in the evolutionary process，and is closely related to OSCA gene of A. thaliana，rice and tomato. Functional differentiation exists within the OSCA gene family in watermelon，and ClaOSCA3 and ClaOSCA5 may be important stress resistance genes in the stress response mechanism.