The purpose of this study was to screen differentially expressed genes and microRNAs in order to find a new target for the accurate diagnosis and effective therapy of alcoholic liver disease (ALD) at the gene and microRNA levels. The total RNA of liver tissues was extracted from four groups of patients, ten subjects each. Microarrays were utilized to detect differentially expressed genes and microRNAs. According to gene values, significance levels and false discovery rate with a random variance model, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, node genes and key microRNAs in networks were obtained and analyzed. A total of 878 differentially expressed genes and 26 microRNAs were found. In co-expression genetic networks, node genes modulating the network were Acyl-coenzyme A synthetase-3 (ACSF3), Frizzled-5 (FZD5), LOC727987 and C1orf222. In microRNA-gene networks, the key microRNAs were hsa-miR-570, hsa-miR-122, hsa-miR-34b, hsa-miR-29c, hsa-miR-922 and hsa-miR-185, which negatively regulated approximately 79 downstream target genes. In the course of ALD, we found 4 differentially expressed node genes and analyzed ACSF3 and FZD5. ACSF3 was significantly upregulated, and was involved in fatty acid and lipid metabolism and accelerated liver injury. These two genes were involved in fatty acids and lipid metabolism. FZD5 was downregulated and reduced the synthesis of membrane transport protein in the hepatic membrane and the membrane stability, and accelerated the liver cell apoptosis process. Six key microRNAs regulated numerous biological functions such as the immune response, the inflammatory response and glutathione metabolism. This finding provides valuable insight into the diagnosis and treatment of ALD.