Patchouli (Pogostemon cablin (Blanco) Benth.) is a plant from the Lamiaceae family. Sesquiterpene hydrocarbons make up the majority of the patchouli oil's > 40 primary constituents, which are found in its essential oils. Plant cytochrome P450 genes are heme-containing monooxygenases enzymes, which involve in both primary and secondary metabolism. To date, analyses of the CYP450 gene family in this sesquiterpenes-producing species has been limited. Here, we identified 142 CYP450 genes in the patchouli, and comparison to the other ten plants revealed that the patchouli had undergone the loss of CYP450 genes after the polyploidization events. This pattern is totally different to that for the terpene synthases, which are much more abundant and are located at the upstream of CYP450 genes in the terpenoids biosynthesis pathway. Phylogenetic analyses grouped CYP450 genes into two main clades: the A-type (CYP71 clan) and the non-A-type (CYP72 clan, CYP85 clan, CYP86 clan, and eight single-family clades). The A-type and non-A-type CYP450 genes included 77 and 65 genes (12 and 26 gene families) in patchouli, respectively. Further, we identified four genes in the CYP71 family, two genes in the CYP81 family, one gene in the CYP82 family, one gene in the CYP85 clan, and one gene in the CYP77 family that are significantly differentially expressed among tissues and their expression levels are significantly correlated to the patchouli oil contents, therefore holding the potential roles in the biosynthesis of sesquiterpenes in the patchouli.