Objective To explore the expressions and clinical significance of acyl coenzyme A -cholesterol acyltransferase 1 (ACAT1) and ACAT2 in patients with colon cancer. Methods The colon cancer, paracancerous and normal colon tissues of 60 patients with colon cancer were collected. PCR and immunohistochemical staining were used to detect the gene and protein expression levels of and in the tissues, and then SPSS20.0 was used to analyze their correlations with clinicopathological indices. Results The gene and protein expressions of and in the colon cancer tissues were higher than those in the paracancerous tissues and the normal colon tissues, and the differences were statistically significant (P < 0.05). The expressions of and genes were correlated to age of the patients, Duke's stage and degree of tumor differentiation; and there was a correlation between the expressions of both genes in the colon cancer tissues (P < 0.05). Conclusions ACAT1 and ACAT2 are highly expressed in colon carcinoma tissues, and their expressions are correlated to some clinical pathological characteristics such as the degree of differentiation of colon cancer and the distant metastasis. Therefore ACAT1 and ACAT2 have potential clinical significance for the early diagnosis of colon cancer.