On January 1, 2019, a new regulation on the control of smoking in public places was officially implemented in Hangzhou, China. On the day of the implementation, a large number of Chinese media reported the contents of the regulation on the microblog platform Weibo, causing a strong response from and heated discussion among netizens.This study aimed to conduct a content and network analysis to examine topics and patterns in the social media response to the new regulation.We analyzed all microblogs on Weibo that mentioned and explained the regulation in the first 8 days following the implementation. We conducted a content analysis on these microblogs and used social network visualization and descriptive statistics to identify key users and key microblogs.Of 7924 microblogs, 12.85% (1018/7924) were in support of the smoking control regulation, 84.12% (6666/7924) were neutral, and 1.31% (104/7924) were opposed to the smoking regulation control. For the negative posts, the public had doubts about the intentions of the policy, its implementation, and the regulations on electronic cigarettes. In addition, 1.72% (136/7924) were irrelevant to the smoking regulation control. Among the 1043 users who explicitly expressed their positive or negative attitude toward the policy, a large proportion of users showed supportive attitudes (956/1043, 91.66%). A total of 5 topics and 11 subtopics were identified.This study used a content and network analysis to examine topics and patterns in the social media response to the new smoking regulation. We found that the number of posts with a positive attitude toward the regulation was considerably higher than that of the posts with a negative attitude toward the regulation. Our findings may assist public health policy makers to better understand the policy's intentions, scope, and potential effects on public interest and support evidence-based public health regulations in the future.