The COVID-19 pandemic has now become very severe as never before due to the overwhelming spread of Omicron. We found that Omicron outbreak can be effectively prevented by inactivated vaccines, which averted an outbreak of more than 1.6 million people in Hangzhou, China. The 36 mutations in the target spike protein of Omicron neutralizing antibody enable it to evade the immune protection afforded by vaccines. This is because that mRNA and adenovirus-vector vaccines are designed to recognize the spike (S) glycoprotein of the SARS-CoV-2 wild-type (WT) strain. However, Inactivated vaccines contain the whole viral antigens and remain stable in their recognition of newly emerging variants of SARS-CoV-2. Our study confirmed the advantage of inactivated vaccines in the face of highly mutated Omicron variant and provided a basis for the development of effective vaccines to prevent future long-term transmission, mutation and recurrence of SARS-CoV-2.