Heterochromatin protein 1 alpha (HP1 alpha) is a gene that mediates chromatin conformation, gene silencing and cancer progression. However, little is known regarding the impact of HP1a in the pathogenesis of cholangiocarcinoma (CCA). In the present study, we demonstrate that HP1 alpha is significantly upregulated in CCA tissues and cell lines, while downregulation of HP1 alpha leads to suppression of cell proliferation. Then we find that downregulation of HP1 alpha can decrease H3K9me3 enrichment and DNA methylation rate of secreted frizzled-related protein 1 (SFRP1) promoter, resulting in restoring the expression of SFRP1. Moreover, restoration of SFRP1 expression can suppress CCA cells proliferation. These results provide a mechanistic understanding of the role of HP1 alpha in the pathogenesis of CCA and may offer a novel therapeutic target in this disease.