Objective: To knockdown the C-erbB2 gene in salivary gland adenoid cystic carcinoma SACC-83 cells using RNA interference, and determine the effect of silencing C-erbB2 on cell proliferation. Methods: C-erbB2-siRNA was transfected into SACC-83 cells. RT-PCR and immunohistochemistry were used to detect C-erbB2 expression in SACC-83 cells. Cell proliferation was measured by the MTT assay and gene knockdown was achieved by RNA interference. Apoptosis was analyzed by flow cytometry. Results: Compared with the control, C-erbB2 mRNA expression was decreased in the C-erbB2-siRNA transfection group, and immunohistochemical analysis indicated that C-erbB2 protein expression was decreased. After C-erbB2-siRNA was transfected for 48 h, absorbance at 570 nm (MTT) was 0.185±0.021 compared with 0.354±0.034, 0.299±0.053, and 0.314±0.049 in the blank control, liposome control and negative control siRNA groups, respectively. The differences were statistically significant (P < 0.05) between the C-erbB2-siRNA group and the control groups. Following the C-erbB2 knockdown, the percentage of apoptotic cells was 5.63% compared with 2.04%, 2.85%, and 2.98% in the three control groups, respectively. Proliferation of SACC-83 cells was inhibited, and early apoptotic cells were increased. Conclusion: RNA interference can effectively silence C-erbB2 gene expression and inhibit growth of SACC-83 cells, which indicates the potential of targeting this gene as a novel gene therapy approach for the treatment of salivary gland adenoid cystic carcinoma.