Translation of mRNA into protein proceeds in three phases: initiation, elongation, and termination. Regulated translation allows the prompt production of selective proteins in response to physiological needs and is often controlled by sequence-specific RNA-binding proteins that function at initiation. Whether the elongation phase of translation can be modulated individually by trans-acting factors to synthesize polypeptides at variable rates remains to be determined. Here, we demonstrate that the RNA-binding protein, cytoplasmic polyadenylation element binding protein (CPEB)2, interacts with the elongation factor, eEF2, to reduce eEF2/ribosome-triggered GTP hydrolysis in vitro and slow down peptide elongation of CPEB2-bound RNA in vivo. The interaction of CPEB2 with eEF2 downregulates HIF-1α RNA translation under normoxic conditions; however, when cells encounter oxidative stress, CPEB2 dissociates from HIF-1α RNA, leading to rapid synthesis of HIF-1α for hypoxic adaptation. This study delineates the molecular mechanism of CPEB2-repressed translation and presents a unique model for controlling transcript-selective translation at elongation.