The universal vaccination against vaccinia across the country is an effective measure to eliminate smallpox. Some cities took the lead in eliminating smallpox， and created replicable organizational experience. This paper investigated the history of epidemic prevention in the largest city in south China at the beginning of the founding of the People’s Republic of China through the continuous reports in Nanfang Daily of the universal vaccination against vaccinia in Guangzhou， and by which， we can understand the government’s decision?making， grass?roots mobilization， public response and the remarkable achievements of Guangzhou’s universal vaccination against vaccinia， so as to provide a unique perspective for investigating urban epidemic prevention.