Objectives To test the feasibility of using Twitter data to assess determinants of consumers' health behavior towards Human papillomavirus (HPV) vaccination informed by the Integrated Behavior Model (IBM). Methods We used three Twitter datasets spanning from 2014 to 2018. We preprocessed and geocoded the tweets, and then built a rule-based model that classified each tweet into either promotional information or consumers' discussions. We applied topic modeling to discover major themes, and subsequently explored the associations between the topics learned from consumers' discussions and the responses of HPV-related questions in the Health Information National Trends Survey (HINTS). Results We collected 2,846,495 tweets and analyzed 335,681 geocoded tweets. Through topic modeling, we identified 122 high-quality topics. The most discussed consumer topic is "cervical cancer screening"; while in promotional tweets, the most popular topic is to increase awareness of "HPV causes cancer". 87 out of the 122 topics are correlated between promotional information and consumers' discussions. Guided by IBM, we examined the alignment between our Twitter findings and the results obtained from HINTS. 35 topics can be mapped to HINTS questions by keywords, 112 topics can be mapped to IBM constructs, and 45 topics have statistically significant correlations with HINTS responses in terms of geographic distributions. Conclusion Not only mining Twitter to assess consumers' health behaviors can obtain results comparable to surveys but can yield additional insights via a theory-driven approach. Limitations exist, nevertheless, these encouraging results impel us to develop innovative ways of leveraging social media in the changing health communication landscape.