Human papillomavirus infections are the most prevalent sexually transmitted disease among women worldwide. Cervical cancer is the second-most frequent disease worldwide in terms of incidence and mortality, and it is primarily responsible for fatalities in low- to middle-income nations, including Ethiopia. To assess awareness, acceptance, and associated factors of the human papillomavirus vaccine among parents of daughters in the Hadiya zone, southern Ethiopia. From November to December 2021, a community-based cross-sectional study was conducted in the Hadiya zone among parents with daughters in the zone. The study respondents were chosen using a two-stage sampling technique from parents with a 9-14-year-old daughter. An interviewer-administered questionnaire was used to collect data. For analysis, the data were entered into Epidata version 3.1 and exported to SPSS version 25. Variables with a -value less than 0.25 in the bivariate analysis were transferred to multivariable analysis. A logistic regression model was applied to forecast the association between the predictor and outcome variables. Statistical significance was considered at a 0.05 -value. The study showed that the overall acceptance of parents to vaccinate their daughters with HPV vaccination was 450 (84.9%). Parents of daughters of male sex (AOR: 0.407; 95%CI: 0.221, 0.748), who had only one daughter (AOR: 2.122; 95%CI: 1.221, 3.685), whose daughter(s) attended a government school (AOR: 0.476; 95%CI: 0.263, 0.861), who had poor knowledge (AOR: 0.532; 95%CI: 0.293, 0.969) and who had a negative attitude (AOR: 0.540; 95%CI: 0.299, 0.977) were discovered to have a strong correlation. This study found that there was a high level of parental acceptance; attitudes and knowledge about the HPV vaccine are significant in determining their intentions to vaccinate their daughter. Authorities in high-risk areas for cervical cancer incidence should plan and implement strategies by providing health information regarding human papillomavirus vaccination with an emphasis on raising community awareness.