Objective To investigate the effect of human papillomavirus (HPV) 16 E6 gene on the expression of E-cadherin (E-cad) in cervical cancer cell line SiHa. Methods HPV16 E6 expression system was established in the cervical cancer cell line SiHa by using transient transfection system, MTT method was used to detect SiHa cell proliferation activity, and reverse transcription-polymerase chain reaction (RT-PCR) and western blot method was used respectively to detect E-cad mRNA and protein expression level in cells after HPV16 E6 transfection. Results Compared with the blank control group (non-transfected plasmid) and the vector group (the addition of pcDNA3.1), the cell viability rate of the E6 group (pcDNA3-1-HPV16 E6) was significantly increased (P<0 .05), while there was no significant difference between the vector group and the blank control group (P>0.05). The relative expressions of E-cad mRNA in the E6 group, the vector group and the blank control group were 0.26±0.12, 0.82±0.14, 0.83±0.21 respectively, then the protein relative expressions in the three groups were 0.62±0.02, 1.33±0.04, 1.31±0.05 respectively. The expressions level of E-cad mRNA and protein in E6 group were significantly lower than those in the other two groups (all P<0.05). However, there was no significant difference between the vector group and the blank control group (both P>0.05). Conclusion The instantaneous transfection of HPV16 E6 gene can reduce the expression of E-cad in cervical cancer cells, which is closely related to the occurrence and development of cervical cancer.