BACKGROUND: The human papillomavirus (HPV) test has emerged as a significant improvement over cytology for primary cervical cancer screening. In Canada, provinces and territories are moving toward implementing HPV testing in cervical cancer screening programs. Although an abundance of research exists on the benefits of HPV-based screening, there is a dearth of research examining women's understanding of HPV testing. In other countries, failure to adequately address women's concerns about changes has disrupted the implementation of HPV-based screening. OBJECTIVE: The aims of the multipart study described in this paper are to develop psychometrically valid measures of cervical cancer screening-related knowledge, attitudes, and beliefs; to examine the feasibility of a questionnaire examining psychosocial factors related to HPV-based screening; and to investigate psychosocial correlates of women's intentions to participate in HPV-based screening. METHODS: We conducted a web-based survey (study 1) of Canadian women to assess the acceptability and feasibility of a questionnaire, including the validation of scales examining cervical cancer knowledge, HPV testing knowledge, HPV testing attitudes and beliefs, and HPV test self-sampling attitudes and beliefs. Preferences for cervical cancer screening were assessed using the best-worst scaling methodology. A second web-based survey (study 2) will be administered to a national sample of Canadian women between June 2022 and July 2022 using the validated scales. Differences in the knowledge, attitudes, beliefs, and preferences of women who are currently either underscreened or adequately screened for cervical cancer will be examined through bivariate analyses. Multinomial logistic regression will be used to estimate the associations between psychosocial and sociodemographic factors and intentions to undergo HPV-based screening. RESULTS: Between October 2021 and November 2021, a total of 1230 participants completed the questionnaire in study 1, and 1027 (83.49%) responses were retained after data cleaning methods were applied. Feasibility was comparable with similar population-based surveys in terms of survey length, participant attrition, and the number of participants excluded after data cleaning. As of May 2022, analysis of study 1 is ongoing, and results are expected to be published in the summer of 2022. Data collection is expected to begin for study 2 in the summer of 2022. Results are expected to be published between late 2022 and early 2023. CONCLUSIONS: Findings will provide direction for Canadian public health authorities to align guidelines to address women's concerns and optimize the acceptability and uptake of HPV-based primary screening. Validated scales can be used by other researchers to improve and standardize the measurement of psychosocial factors affecting HPV test acceptability. Study results will be disseminated through peer-reviewed journal articles; conference presentations; and direct communication with researchers, clinicians, policy makers, media, and specialty organizations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38917.