Hepatitis B virus (HBV) and Hepatitis C virus (HCV) is major public health problems that affect million people worldwide and people who are infected assumed to develop liver cirrhosis or hepatocelular carcinoma. Screening of blood donors is essential for healthy and safe donation. A cross sectional study design was conducted among volunteer blood donors in Arba Minch blood bank from March 2015 to April 2015. A total of 359 volunteer blood donors who came to Arba Minch blood Bank were interviewed face to face, then data was collected by using structured and pre-tested questionnaire, and finally blood sample drown and tested for HBV and HCV by using ELISA (enzyme linked immunosorbent assay) technique. Descriptive statistics was calculated for most variables in the study. OR and 95% CI was used to assess the association. Prevalence of HBV and HCV among study participant was 4.7 and 0%, respectively. From 17 participants tested positive for HBV, 8 (47%) were males. The test positivity among male was 8/197 (4.1%) while among females was 9/162 (5.6%) and more than three forth participants tested positive were age less than 25. After multivariate analysis, when positivity was compared among study participants grouped based on average monthly income, participants earning 581-1,300 birr were 32.2% less likely to have infection than participants earning below 580 birr per month. (AOR = 0.322, 95%CI =0.108-0.961). Volunteer donors who exposed to unsafe therapeutic drug injection was 8(2.2%) and from those 3(37.5%) was positive for HBV. When compare to volunteers who did not exposed 14(4%), exposed donors 11 times increased risk of HBV infection. This was statistically significant (AOR = 11.090, p = 2.258-54.475). Prevalence HBV of among volunteer blood donors in Arbaminch Blood Bank was 4.7%. Low monthly income and using unsafe therapeutic injection were related to HBV infection.