Avian influenza virus (AIV) is a type A virus of the family Orthomyxoviridae and its outbreaks not only cause economic losses in poultry, but also are worldwide threats to human health. The phenotypic changes in host cells induced by pathogens are always accompanied by remarkable changes in gene expression. Therefore understanding the gene expression profile of infected cells at the global level is important to get insights into interactions between hosts and viruses. Different genomic approaches have been utilized in the current study to investigate the host-AIV interactions in chickens. The Ser to Asn mutation on position 631 in the chicken Mx1 protein was reported to result in a positive antiviral function in vitro. With AIV infection, the Mx1 mRNA expression levels in heterozygous birds were significantly up-regulated. Additional mutations on the chicken Mx1 coding region were identified by sequencing. The results showed that most identified mutations were co-segregated with S631N mutation except one insertion in the position of 1544bp in the heterozygous birds. We speculate this insertion might be related to the up-regulation of mRNA expression of heterozygous birds with AIV infection. The miRNAs play critical roles in biological processes and are important effectors in host-pathogen interactions. The miRNA deep sequencing was used to profile miRNAs in AIV infected or non-infected chickens. Differentially expressed miRNAs identified have expanded our knowledge in the functions of these potential immune related chicken miRNAs regulating host response to AIV infection. Both microarray and transcriptome analysis by RNA-Seq were used in the current study to investigate the global gene expression of host response to AIV infection. Through the comprehensive analysis, a list of strong candidate miRNAs such as miR-32 and their host target genes including Mx1 were identified for further elucidating the regulatory mechanism of host-AIV interaction. In summary, we have identified many important candidate host genes and miRNAs which play important roles in the modulation of host response to AIV infection using genomic approaches. Further investigation of underline regulatory mechanisms of these genes, miRNAs or related pathways, followed by functional analysis, could lay solid foundation for understanding cellular and molecular mechanisms of the host-AIV interactions, thereby, pave a way for the development of novel protective strategies against AIV infection in chickens.