Caleosin is a kind of protein involved in oil body synthesis. In this study, the PfClo1 and PfClo2 gene fragments were obtained from perilla transcriptome database. The PfClo2 gene was almost not expressed in various perilla tissues, hence the PfClo1 gene was cloned and analyzed by qRT-PCR to investigate the expression characteristics of the gene PfClo1 in different perilla varieties and its response to drought stress. The results of PfClo1 gene sequence analysis showed that the full-length ORF sequence of PfClo1 gene was 609 bp, encoding 202 amino acids, the theoretical isoelectric point was 5.19 and the hydrophilicity coefficient was 0.678. The PfClo1 protein was located in the cytoplasm from our prediction by using PSORT software. The PfClo1 protein had high similarity with caleosin sequence of Salvia miltiorrhiza and Sesamum indicum by blast homologous sequence alignment analysis, and belonged to a typical caleosin family member. The results of qRT-PCR analysis showed that PfClo1 gene was expressed in flowers and seeds of ‘Jinzisu 1’, and the expression level reached the highest in seeds 30 days after flowering. By analyzing the differential expression of different perilla varieties, it was found that the PfClo1 gene expression was positively correlated with the oil formation of perilla seeds. After the ‘Jinzisu 1’ seedlings were treated with 20% PEG, it was found that the expression level of PfClo1 gene reached the highest at 12 h of stress treatment, which was 6.78 times that of the control. It is speculated that this gene may play a regulatory role in the induction of drought stress in perilla. The results provide a theoretical basis for further exploring the function of PfClo1 gene during perilla seed development and response to drought stress.