Marek’s disease (MD) is a neoplastic disease in chickens, caused by an oncogenic and highly contagious cell-associated herpesvirus, Marek’s disease virus (MDV). It is almost a century since the first description of Marek’s disease, and the massive progress in genetics enables explorations for the in-depth characterization of genetic basis of MDV lifecycle and the molecular events of tumor formation and dissemination. To investigate host genetic resistance to MDV, we conducted a genome-wide association study (GWAS) with MDV-infected chickens including susceptible chickens (cases) and resistant chickens (controls). After scanning 38,655 valid genomic markers, two SNPs were found to be associated with host resistance to MDV. The first one, located in the chromosome 2, reached the genome-wide significance level (P = 2.97E-02, Bonferroni correction, OR=0.080). The second, located in the chromosome 5, reached the chromosome-wide significance level (P = 8.62E-03, Bonferroni correction, OR=0.1068). In order to confirm the GWAS result, we used qPCR to detect the expression patterns of genes containing the significant SNP in spleens. The expression of the gene on GGA5 was significantly reduced (P<0.05) in the case group compared with the controls, while the expression of the gene on GGA2 didn’t show a significant change between the case and control group.