Addiction, a disorder of maladaptive brain plasticity, is associated with changes in numerous gene expressions. Nowadays, high-throughput sequencing data on addictive substance-induced gene expression have become widely available. A resource for comprehensive annotation of genes that show differential expression in response to commonly abused substances is necessary. So, we developed AddictGene by integrating gene expression, gene-gene interaction, gene-drug interaction and epigenetic regulatory annotation for over 70,156 items of differentially expressed genes associated with 7 commonly abused substances, including alcohol, nicotine, cocaine, morphine, heroin, methamphetamine, and amphetamine, across three species (human, mouse, rat). We also collected 1,141 addiction-related experimentally validated genes by techniques such as RT-PCR, northern blot and in situ hybridization. The easy-to-use web interface of AddictGene (http://159.226.67.237/sun/addictgedb/) allows users to search and browse multidimensional data on DEGs of their interest: 1) detailed gene-specific information extracted from the original studies; 2) basic information about the specific gene extracted from NCBI; 3) SNP associated with substance dependence and other psychiatry disorders; 4) expression alteration of specific gene in other psychiatric disorders; 5) expression patterns of interested gene across 31 primary and 54 secondary human tissues; 6) functional annotation of interested gene; 7) epigenetic regulators involved in the alteration of specific genes, including histone modifications and DNA methylation; 8) protein–protein interaction for functional linkage with interested gene; 9) drug-gene interaction for potential druggability. AddictGene offers a valuable repository for researchers to study the molecular mechanisms underlying addiction, and might provide valuable insights into potential therapies for drug abuse and relapse.