<jats:title>Abstract</jats:title> <jats:p>Altered glutamine metabolism is emerging target of cancer therapy. Glutamine deprivation has been proposed to induce apoptosis in multiple cancers. Dependency on glutamine metabolism of skw 6.4 lymphoma cell was investigated in vitro and in vivo. Glutamine deprivation induces apoptosis of skw 6.4 cell. Intracellular concentration of metabolites in tricarboxylic acid cycle and glutathione concentration were reduced and concentration of reactive oxygen species (ROS) and expression of PP2A were increased in glutamine-deprived skw6.4 cell. Reduction of ROS by antioxidants and knockdown of PP2A inhibited apoptosis induced by glutamine deprivation. Glutamine antagonist reduces skw6.4 tumor size in mouse xenograft model in PP2A-dependent manner. Overall, these results suggest survival of skw6.4 cells depends on the supply of glutamine in PP2A-dependent manner.</jats:p>