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<i>Toxocara canis</i> is a neglected zoonotic roundworm distributed all over the world, causing toxocariasis in humans and animals. However, so far, the immune mechanism of <i>T. canis</i> infection in definitive hosts remains to be clarified. In this study, the transcriptional alterations of Beagle dogs’ peripheral blood mononuclear cells (PBMCs) induced by <i>T. canis</i> infection during the lung infection period were analyzed using RNA-seq technology. A total of 2142 differentially expressed genes were identified, with 1066 upregulated genes and 1076 downregulated genes. Many differentially expressed genes participated in the biological process of intracellular signal transduction, as well as the immune- or inflammation-related KEGG signaling pathway, such as the Notch signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway, through KEGG enrichment analysis. This study indicated that <i>T. canis</i> infection could suppress the biological function of Beagle dogs’ PMBCs and provided basic data to further clarify the interaction mechanism between <i>T. canis</i> and host immune cells.