Background: Clinical practice experiences are critically important to determine that graduate students are expected to achieve the maximum level of clinical competence after receiving necessary and adequate theoretical and practical instructions. However graduates have problems in doing some easy duties. Thus, this study is designed to assess factors affecting clinical practice competence of undergraduate health science student, Hawassa University, South, Ethiopia, 2015.Methods: Institutional based Cross-sectional study was conducted in health science students of Hawassa university referral hospital from April to May 2015 by using structured questionnaire and Focus Group Discussion. Simple random sampling was applied to select study subject among 345 students. Data were entered using Epi Info version 3.5.1 was exported and analyzed by SPSS version 20. Bivariate and multivariate logistic regressions were used to identify independent predictors and for qualitative data, ideas were summarized and analyzed in the form of themes. Result: The prevalence of clinical practice competency from the study participant was 87 (25.2%). Students with adequate clinical case in practical placement were 4 times clinically competent than those students with inadequate clinical case in practical placement with (AOR=3.958, 95% CI 1.238, 12.65).Students with clinical instructor support were clinically competent by 2 times with (AOR=2.064, 95% CI 1.042, 3.694) than students with no clinical instructor support.Conclusion and Recommendation: Clinical instructor support, adequate clinical case in practical placement, use continuous assessment checklist and integration of three learning domain were factors affect clinical practice competency of the students. So improving supervision of clinical instructors, appropriate selection of clinical site and design appropriate clinical practice protocol has important to enhance clinical practice competency of students.