The unicellular photosynthetic model organism cyanobacterium Synechocystis sp. PCC6803 can grow photoautotrophically using CO2 or heterotrophically using glucose as the sole carbon source. Several pathways are involved in carbon metabolism in Synechocystis, and the concerted regulation of these pathways by numerous known and unknown genes is critical for survival and growth of the organism. Here, we report that a hypothetical protein encoded by the open reading frame slr0110 is necessary for heterotrophic growth of Synechocystis. The slr0110-deletion mutant is defective in glucose uptake, heterotrophic growth, and dark viability without detectable defect in autotrophic growth, whereas the level of photosystem II and the rate of oxygen evolution are increased in the mutant. Quantitative proteomic analysis reveals that several proteins in glycolysis and oxidative pentose phosphate pathway are downregulated while proteins in photosystem II and phycobilisome are significantly upregulated in the mutant. Among the downregulated proteins are glucose transporter, glucokinase, glucose-6-phosphate isomerase, and glucose-6-phosphate dehydrogenase and its assembly protein OpcA, suggesting that glycolysis, oxidative pentose phosphate, and glycogen synthesis pathways are significantly inhibited in the mutant, which were further confirmed by enzymatic assays and quantification of glycogen content. These findings established Slr0110 as a novel central regulator of carbon metabolism in Synechocystis, and shed a light on uncovering an intricate mechanism whereby photosynthesis and carbon metabolism are well concerted to survive the crisis when one or more pathways of the system are impaired.