Bone cancer pain (BCP) is refractory to currently available clinical treatment owing to its complicated underlying mechanisms. Studies found that extracellular matrix molecules can participate in the regulation of chronic pain. Decorin is one of the most abundant extracellular matrix molecules, the present study evaluated the effect of decorin on the development of BCP. We found that decorin was upregulated in the L4-6 spinal dorsal horn of the BCP rats. Spinal microinjection of a decorin-targeting RNAi lentivirus alleviated BCP-induced mechanical allodynia and reduced the expression of pGluR1-Ser831 in the BCP rats. Meanwhile, decorin knockdown impaired the excitatory synaptogenesis in cultured neurons and prevented the clustering and insertion of pGluR1-Ser831 into postsynaptic membranes. Taken together, the results of our study suggested that decorin contributes to the development of BCP possibly by regulating the activity of excitatory synaptic molecules in the spinal cord. Our findings provide a better understanding of the function of decorin as a possible therapeutic target for alleviating BCP.