Emerging evidence has suggested a potential role for long non-coding RNAs (lncRNAs) in transcriptome dysregulation during Mycobacterium tuberculosis (Mtb) infection. Understanding the regulatory functions of lncRNAs can provide further insight into the interaction between Mtb and the host. In this study, we sought to explore the lncRNA signature in the Mtb-infected THP1 macrophages (H37Rv, H37Ra, and BCG strains) using the publicly available RNA sequencing dataset of GSE162729. Our analysis identified 6202 putative lncRNAs, with the majority being novel lncRNAs, indicating their significant involvement in the Mtb-infected macrophages. We also identified several differentially expressed lncRNA genes specifically induced in each infected group. Reactome enrichment pathway analysis on cis target genes of lncRNAs revealed that inflammatory immune responses were the predominant features of lncRNAs induced during the H37Rv infection compared to H3Ra and BCG infection. Scavenging by class A receptors and inflammasomes were also highlighted as the common enriched terms among Mtb- and BCG-infected groups. Moreover, we highlighted several potential lncRNAs as hub genes in the predicted regulatory network between the differentially expressed lncRNAs and miRNAs in Mtb-infected THP-1 cells. These findings suggested a possible diverse regulatory role for lncRNAs in the macrophage response to different Mycobacterium strain infections. Further functional study of the lncRNA genes in Mtb infection, while considering the genetic background of the Mtb strain, will be a promising focus for future research.