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Abstract Objective The objectives of the study were to assess attitudes toward epilepsy among medical staffs from basic-level hospitals in southern China and identify significant predictive factors for future stigma reduction interventions. Methods The Public Attitudes Toward Epilepsy (PATE) scale, a two dimensional 14-item scale addressing two major domains: general domain and personal domain, was administered to 448 medical staffs from basic-level hospitals in southern China. Positively stated items in the PATE scale were reversely scored; in this case, a higher score would indicate a more negative attitude. Also, we compared the overall score and per-item scores of the medical staffs versus those of the general population reported in the previous studies using the same scale. Results The cumulative score of the medical staffs was 41.65 ± 6.99, which is significantly lower as compared with 51.38 ± 6.80 of the general population (t (645) = − 16.473, p < 0.001). The general average score (t (645) = − 16.473, p < 0.001) and the mean score in the general domain (t (645) = − 22.573, p < 0.001) of the PATE scale were both significantly lower in the medical staffs compared with the general population, whereas there was no significant difference between the two groups in the personal domain (t(645) = − 0.180, p = 0.857). Age or years in clinical practice, specialty, and title had a significant impact on both the general domain and personal domain. Residence was the only factor found affecting the medical staffs' attitudes toward epilepsy in the personal domain but not in the general domain. Conclusion Medical staffs from basic-level hospitals in southern China demonstrate significant positive attitudes toward people with epilepsy in general aspects when compared with the general population. However, they still showed negative and conservative attitudes when it comes to the personal domain. Future strategies for stigma-reducing public interventions could focus on increasing better understanding of epilepsy among medical staffs in basic-level hospitals in China. Highlights • Medical staffs' attitudes may directly affect mental health of patients with epilepsy. • Medical staffs' attitudes are more positive in the general aspects but not in the personal domain. • Age or years in clinical practice, specialty and title had a significant impact on attitudes among medical staffs. • Residence was the only factor found affecting medical staffs'attitudes toward epilepsy in the personal domain. [ABSTRACT FROM AUTHOR]