The objective of this study was to explore the link between long non-coding RNAs (lncRNAs) and resistance mechanism of albendazole in Haemonchus contortus by analyzing the gene expression profile of lncRNA in sensitive and resistant strains. This study provided the base for the resistance mechanism of Haemonchus contortus. In this experiment, the cDNA sequencing libraries were collected constructed for the sensitive and resistant strains of Haemonchus contortus, and the sequencing was performed using Illumina HiSeq 4000 platform, and differentially expressed lncRNAs (DEIncRNAs) were screened. Then the cis-targeted and trans-targeted genes of DElncRNAs were predicted, and the GO enrichment, KEGG pathway enrichment analysis were also made. The results displayed that 6 377 and 6 356 candidate lncRNA transcripts of sensitive and resistive strains were respectively obtained, 168 DElncRNAs of which were selected. Compared with resistive strains, there were 92 up-regulated and 76 down-regulated lncRNAs in sensitive strains. Meanwhile, 416 candidate target genes of DElncRNAs were obtained. The analytical results indicated that these genes participated in 641 GO terms and 92 signal pathways. The pathways involved in drug resistance are drug metabolism-other enzymes, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450 and so on. In conclusion, these findings inferred that some lncRNA-mediated target genes were associated with the resistance of Haemonchus contortus, and lncRNA may play an important role in the resistance of Haemonchus contortus. This study explored the expression profile of lncRNA in the Haemonchus contortus of sensitive and resistant strains. It was found that DElncRNAs in the sensitive and resistant strains, which helped to find out the Haemonchus contortus resistance mechanism of albendazole and provided a scientific basis for exploring the mechanism of resistance to Haemonchus contortus.