The in silico approach to explore the anti-obesity effects of puerarin suggested that the top 10 hub genes, including TNF, EGFR, MMP9, AKT1, PIK3CA, HIF1A, PRKCZ, TP53, ESR1, and ETGS2, may be the treatment target genes with anti-obesity effects. Here, HIF1A is linked to obesity due to melanocortin 4 receptor deficiency.