A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cel-lular context in order to reveal potential on-target or off-target effects.Recently,the fast accumulation of gene transcriptional profiling data provides us an unprece-dented opportunity to explore the protein targets of chemical compounds from the perspective of cell tran-scriptomics and RNA biology.Here,we propose a novel Siamese spectral-based graph convolutional network(SSGCN)model for inferring the protein targets of chemical compounds from gene transcriptional profiles.Although the gene signature of a compound perturba-tion only provides indirect clues of the interacting tar-gets,and the biological networks under different experiment conditions further complicate the situation,the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles.On a benchmark set and a large time-split validation dataset,the model achieved higher target inference accuracy as compared to previ-ous methods such as Connectivity Map.Further exper-imental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound,or reversely,in finding novel inhibitors of a given target of interest.