Andrographis paniculata, a traditional bulk herb known as a natural antibiotic, is widely cultivated in tropical and subtropical regions. The basic helix-loop-helix (bHLH) transcription factors (TFs) act in a variety of physiological processes in plants, such as plant development, secondary metabolism and abiotic stress responses. There has been no report so far in the research on the bHLH gene family in A. paniculata. In our study, genome-wide analysis was performed for the A. paniculata bHLH (ApbHLH) gene family, and a total of 122 ApbHLH genes (ApbHLHs) were identified, which were renamed on the basis of their physical locations on the chromosomes and the contig numbers. They were classified into 26 subfamilies through phylogenetic analysis, validated by analyses of conserved motifs and gene structures. Subsequently, chromosome distribution, cis-regulatory elements (CREs), syntenic analysis and gene expression profiling were undertaken. The ApbHLHs were randomly distributed on 24 chromosomes, of which three ApbHLHs were localized on unassembled scaffolds. Gene duplication events indicated that ApbHLHs were mainly subject to strong purifying selection during evolution and were affinely closer to dicotyledons, especially Sesamum indicum and Solanum lycopersicum. In addition, the qRT-PCR results revealed that ApbHLHs had specific expression profiles under salinity, salicylic acid (SA) and 6-benzylaminopurine (6-BA) treatments, especially ApbHLH47 and ApbHLH109, which were significantly down-regulated under all three treatments. It implies that they have essential functions in response to abiotic stresses and plant development, and thus can be considered as candidate regulatory factors for further study.