As a novel emerging pathogen, mainly causing visceral and articular gout in goslings, the pathogenesis of goose astrovirus (GAstV) remains unclear, seriously impeding the development of effective prevention and control methods. To better understand the reprogrammed cellular genes due to GAstV infection, a high-throughput transcriptome analysis was performed with primary goose embryo fibroblasts (GEF) at 48 h after infection. A total of 2324 differentially expressed genes (DEGs) were identified, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most DEGs were closely associated with immune signal pathway and metabolic process. Subsequently, several immune and metabolic related genes, such as Mx, OAS, STAT1, IFIT5, and ADA, were identified and further validated via quantitative real-time PCR and western blot. This was the first study using GEF as the cell model to explore the host response to GAstV infection, which will undoubtedly provide a solid foundation to elucidate the pathogenesis of GAstV.