Background: HPV vaccination is the key measure to prevent cervical cancer, but uptake in China lags behind global targets. Understanding Chinese guardians’ preferences is key to improving vaccine acceptance and coverage. Methods: A nationwide online discrete choice experiment survey was conducted among 4933 Chinese guardians across seven provinces in 2022 to quantify preferences and willingness to pay. Attributes included effectiveness, safety, duration, valency, location, and out-of-pocket cost. Results: Out of the 4933 guardians who participated in the study, 4179 (84.72%) were mothers. More than 60% of the guardians belonged to the age group of 35–44 years. Additionally, over half of the respondents (53.15%) had daughters between the ages of 9 and 14 years. Respondents were open to accepting the HPV vaccine with 95% efficacy and exceptional safety. Guardians expressed a preference for longer protection duration (specifically 15 years (βa = 0.340, 95% CI: 0.31, 0.37)) and higher vaccine valency. As for willingness to pay, the respondents placed the highest value on vaccine efficacy, being willing to shell out more than USD 1100 for 95% protection as compared to 50%. Furthermore, very good safety commanded a premium of over USD 800 when compared to average safety. When it comes to willingness to uptake, a vaccine with 95% efficacy led to a more than 35% increase in acceptance as compared to one with 50% efficacy. Similarly, exceptional safety resulted in an increased willingness to uptake of over 25% when compared to average safety. Conclusions: The DCE highlighted effectiveness, safety, and durability as critical drivers of HPV vaccine acceptance, but substantial barriers persist regarding adolescent female coverage in China.