Cystic Echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosing CE primarily relies on imaging techniques, and there is a crucial need for an objective laboratory test to enhance the diagnostic process. Today, cell-free DNAs (cfDNAs) have gained importance regarding their biomarker potential. This study aims to investigate the diagnostic capabilities of different cfDNA targets (Echinococcus-specific repeat sequences (mgs-4 and mgs-12) and partial fragment of repetitive sequence (EG1 Hae III)) and evaluate their diagnostic effectiveness when compared to a frequently used commercial E.granulosus-specific IgG ELISA. Seventy-six confirmed hepatic CE patients and healthy controls were included in the study. The EG1 Hae III region was assessed using nested PCR, whereas real-time PCR was employed to investigate other cfDNA targets. Analysis of the cfDNA-targeted tests indicated that mgs-4 demonstrated the highest diagnostic efficacy in distinguishing CE patients from healthy controls, achieving a sensitivity of 60.5% (p = 0.002). Combining ELISA with the mgs-4 target led to an increased sensitivity of 72.4% for distinguishing between CE patients and the control group. The sensitivity rates for ELISA and the three cfDNA targets varied among the groups. Active CE patients showed sensitivity rates of 52.9%, 52.9%, 23.5%, and 52.9% for ELISA, mgs-4, mgs-12, and EG1 Hae III assays, respectively. In contrast, inactive cyst patients displayed sensitivity rates of 21.4%, 66.7%, 19%, and 42.9% for the corresponding assays. The mgs-4, either alone or in combination with ELISA, demonstrated notably higher sensitivity values for CE diagnosis in all group comparisons compared to serology.