The study evaluated the compliance and acceptability of a new cervical self-sampling device for HPV genotyping for cervical cancer screening among women in Shanghai. Women underwent sequential sampling: self-sampling followed by physician sampling, with both samples analyzed using standardized protocols. Self-collection showed excellent agreement with physician collection (κ = 0.937; 95% CI: 0.89–0.98), with a sensitivity of 91.4% (95% CI: 83.2–96.5%), a specificity of 100% (95% CI: 98.2–100%), an accuracy of 97.5% (95% CI: 94.8–99.0%), with a positive predictive value of 100% and a negative predictive value of 96.5% (95% CI: 93.2–98.5%). Of the 268 women, 41.4% initially preferred self-collection, the share rose to 56.7% when costs were taken into account. The main reasons for preference were the convenience of home collection (59.2%), reduction of pain through self-controlled pressure (57.2%) and privacy (56.6%). Multivariate analysis showed associations with age (p < 0.0001), HPV vaccination status (p = 0.0064), previous screening experience (p = 0.0064), and perceived comfort (p < 0.0001). The device supports increased screening coverage through privacy, convenience and cost-effectiveness.