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Houttuynia cordata Thunb., commonly known as yuxingcao in China, is known for its characteristic fishy smell and is widely recognized as an important herb and vegetable in many parts of Asia. However, the lack of genomic information on H. cordata limits the understanding of its population structure, genetic diversity, and biosynthesis of medicinal compounds. Here we used single-molecule sequencing, Illumina paired-end sequencing, and chromosome conformation capture technology to construct the first chromosome-scale decaploid H. cordata reference genome. The genome assembly was 2.63 Gb in size, with 1348 contigs and a contig N50 of 21.94 Mb further clustered and ordered into 88 pseudochromosomes based on Hi-C analysis. The results of genome evolution analysis showed that H. cordata underwent a whole-genome duplication (WGD) event ~17 million years ago, and an additional WGD event occurred 3.3 million years ago, which may be the main factor leading to the high abundance of multiple copies of orthologous genes. Here, transcriptome sequencing across five different tissues revealed significant expansion and distinct expression patterns of key gene families, such as l-amino acid/l-tryptophan decarboxylase and strictosidine synthase, which are essential for the biosynthesis of isoquinoline and indole alkaloids, along with the identification of genes such as TTM3 , which is critical for root development. This study constructed the first decaploid medicinal plant genome and revealed the genome evolution and polyploidization events of H. cordata ., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)