Abstract: In order to study the disease resistance mechanism of Guizhou white goats against Haemonchus contortus and to discover relevant important regulatory factors, the experiment used transcriptome sequencing method to study the blood of Guizhou white goats naturally infected with Haemonchus contortus;differentially expressed genes in the blood of the experimental group and the control group were analyzed using bioinformatics methods, and related gene regulatory pathways were constructed. The results showed that a total of 121 differentially expressed genes were obtained, and there were 75 down-regulated genes in the experimental group. Most of down-regulated genes were mitochondrial-related genes（ND1,ND4,COX3）. The expression of ND1,ND4 genes was extremely significantly down-regulated（P＜0.01）,and the expression of COX3 gene was significantly down-regulated（P＜0.05）. The GO function enrichment analysis and KEGG signal pathway analysis of down-regulated expressed genes were carried out. These down-regulated expressed genes were divided into three categories and 38 groups. A total of 8 pathways were found. Among them, the most significant gene enrichment was genetic information processing, energy metabolism and oxidative phosphorylation, which is mitochondria-related signal pathways. Mitochondrial dysfunction was mainly manifested in energy metabolism disorders. The results suggested that the changes in the expression or function of these genes may be caused by the infection of Haemonchus contortus which led to host anemia and local abomasum inflammation, and participated in the inflammation regulation process.