GCN5-related N-acetyltransferases (GNAT) family proteins are a diverse group of lysine acetyltransferases (KATs) widespread in bacteria. The members of this superfamily exhibited significant influences in many cellular processes, such as DNA binding, enzymatic activity, protein-protein interactions, protein stability, or protein localization. Streptococcus mutans is the crucial pathogen of human dental caries, however, the function of acetyltransferases in S. mutans remains unknown. In this study, we found that SMU.1558c, a member of the GNAT super-family, affects the growth rate, biofilm formation and extracellular polysaccharides (EPS) synthesis in S. mutans. When compared with the parental strain, a total of 166 differentially expressed proteins (DEPs) (>1.2-fold) were identified in the smu.1558c deletion mutant by global protein expression profiling. Bioinformatics analysis indicated that the DEPs were mainly related to protein homeostasis maintenance, carbohydrate metabolism and substances transporter systems.