Objective To explore whether mutations of p53 gene and hMLH1 gene may be an early event of carcinogenesis in rectal cancer. Methods The expressions of p53 and hMLH1 protein in 32 patients with early rectal cancer, 32 patients with rectal adenoma， and 30 patients with normal rectal mucosa were detected by PV-9000 immunohistochemical method between February 2003 and July 2009 in this hospital. Results ① The positive expression rates of p53 protein were 0 (0/30), 59.38% (19/32), and 68.75% (22/32) in the normal rectal mucosa, rectal adenoma, and early rectal cancer, respectively. There was no difference between the rectal adenoma and early rectal cancer (Pgt;0.05), but which were higer than that of the normal rectal mucosa (Plt;0.01). The negative expression rates of hMLH1 protein were 0 (0/30), 12.50% (4/32), and 50.00% (16/32) in the normal rectal mucosa, rectal adenoma, and early rectal cancer, respectively. The negative expression rate of hMLH1 protein in the early rectal cancer was significantly higher than that in the rectal adenoma or the normal rectal mucosa (Plt;0.01). ② The positive expression of p53 concomitant negative expression of hMLH1 in the rectal adenoma and early rectal cancer were 9.38% (3/32) and 37.50% (12/32), respectively, the difference was statistically significant (P=0.008). ③ In the early rectal cancer, the positive expression of p53 and the negative expression of hMLH1 were closely related to the degree of differentiation (Plt;0.05), but which weren’t related to the patient’s gender, age, tumor maximum diameter, depth of invasion or fecal occult blood (Pgt;0.05). ④ The positive expression of p53 was closely related to higher adenoma hyperplasia (P=0.009), while not of negative expression of hMLH1 (Pgt;0.05). Conclusion Simultaneous mutations of p53 gene and hMLH1 gene may be an early event of carcinogenesis in rectal cancer.