Background: Cancer ranks among the most serious public health challenges worldwide. In China—the world’s most populous country—about one-quarter of the population consists of people with cancer. Social media has become an important platform that the Chinese public uses to express opinions. Objective: We investigated cancer-related discussions on the Chinese social media platform Weibo (Sina Corporation) to identify cancer topics that generate the highest levels of user engagement. Methods: We conducted topic modeling and regression analyses to analyze and visualize cancer-related messages on Weibo and to examine the relationships between different cancer topics and user engagement (ie, the number of retweets,...