Viral diseases of honeybees are a major challenge for the global beekeeping industry. Chinese indigenous honeybee (Apis cerana cerana, Acc) is one of the major Asian honeybee species and has a dominant population with more than 3 million colonies. However, Acc is frequently threatened by a viral disease caused by Chinese sacbrood virus (CSBV), which leads to fatal infections and eventually loss of the entire colony. Nevertheless, knowledge on the pathological mechanism of this deadly disease is still unknown. Here, an integrated gel-based and label-free liquid chromatography-mass spectrometry (LC-MS) based proteomic strategy was employed to unravel the molecular event that triggers this disease, by analysis of proteomics and phosphoproteomics alterations between healthy and CSBV infected worker larvae. There were 180 proteins and 19 phosphoproteins which altered their expressions after the viral infection, of which 142 proteins and 12 phosphoproteins were down-regulated in the sick larvae, while only 38 proteins and 7 phosphoproteins were up-regulated. The infected worker larvae were significantly affected by the pathways of carbohydrate and energy metabolism, development, protein metabolism, cytoskeleton, and protein folding, which were important for supporting organ generation and tissue development. Because of abnormal metabolism of these pathways, the sick larvae fail to pupate and eventually death occurs. Our data, for the first time, comprehensively decipher the molecular underpinnings of the viral infection of the Acc and are potentially helpful for sacbrood disease diagnosis and medicinal development for the prevention of this deadly viral disease.