The aim of the present study was to detect the expression levels of FERM domain-containing 4A (FRMD4A) in rectal cancer tissues and peripheral blood and to investigate the correlation between FRMD4A and cancer development. A total of 78 consecutive patients were enrolled in this study. Thirty healthy individuals were used as the control group. The expression of FRMD4A in rectal cancer and the corresponding normal adjacent tissues was detected by immunohistochemistry and western blotting. The expression of FRMD4A mRNA in peripheral blood was detected by reverse transcription-quantitative polymerase chain reaction. The expression of FRMD4A in rectal cancer tissues was found to be negatively correlated with the degree of differentiation, depth of invasion and Dukes' stage. A negative correlation was identified between FRMD4A and epithelial cadherin expression. The expression of FRMD4A in the peripheral blood of patients with rectal cancer was significantly increased compared with that in the control group (P<0.05). Expression of FRMD4A in the peripheral blood in the patients with lymph node metastasis was significantly increased compared with that in the patients without lymph node metastasis (P<0.05). These results indicate that the expression of FRMD4A is significantly increased in rectal cancer tissues and the peripheral blood of patients with rectal cancer, and the expression levels of FRMD4A are closely associated with differentiation, invasion of rectal cancer and Dukes' stage. In conclusion, the findings of the present study suggest that FRMD4A may be used as a target for the diagnosis and treatment of rectal cancer.