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HVA22 family proteins with a conserved TB2/DP1/HVA22 domain are ubiquitous in eukaryotes. <i>HVA22</i> family genes have been identified in a variety of plant species. However, there has been no comprehensive genome-wide analysis of <i>HVA22</i> family genes in tomato (<i>Solanum lycopersicum</i> L.). Here, we identified 15 non-redundant <i>SlHVA22</i> genes with three segmentally duplicated gene pairs on 8 of the 12 tomato chromosomes. The predicted three-dimensional (3D) models and gene ontology (GO) annotations of SlHVA22 proteins pointed to their putative transporter activity and ability to bind to diverse ligands. The co-expression of <i>SlHVA22</i> genes with various genes implicated in multiple metabolic pathways and the localization of SlHVA22-GFP fused proteins to the endoplasmic reticulum suggested that they might have a variety of biological functions, including vesicular transport in stressed cells. Comprehensive expression analysis revealed that <i>SlHVA22</i> genes were differentially expressed in various organs and in response to abiotic stress conditions. The predominant expression of <i>SlHVA22i</i> at the ripening stage and that of <i>SlHVA22g</i>, <i>SlHVA22k</i>, and <i>SlHVA22l</i> in fruits at most developmental stages suggested their probable involvement in tomato fruit development and ripening. Moreover, the transcript expression of most tomato <i>HVA22</i> genes, particularly <i>SlHVA22b</i>, <i>SlHVA22i</i>, <i>SlHVA22k</i>, <i>SlHVA22l</i>, <i>SlHVA22m</i>, and <i>SlHVA22n</i>, was affected by abscisic acid (ABA) and diverse abiotic stress treatments, indicating the likely involvement of these genes in tomato abiotic stress responses in an ABA-dependent manner. Overall, our findings provide a foundation to better understand the structures and functional roles of <i>SlHVA22</i> genes, many of which might be useful to improve the abiotic stress tolerance and fruit quality of tomato through marker-assisted backcrossing or transgenic approaches.