BACKGROUND: Following advances in treatment for hepatitis C (HCV), optimizing linkage to care and adherence to treatment of people who inject drugs became of pivotal importance. An ECDC/EMCDDA stakeholders survey in 2018 indicated that two components of the cascade of care, linkage to care and adherence to treatment, were priority areas for inclusion in the updated guidance, planned for publication in 2022. This systematic review was commissioned with the aim to evaluate the effectiveness of interventions on HCV linkage to care and adherence to treatment among people who inject drugs. *** METHODS: The full study protocol is available at PROSPERO (2020 CRD42020191116). We searched five databases to identify studies published between 2011 and 2020. Studies were included if they had a comparative study design and reported on the primary outcomes for linkage to care (visits, treatment initiation) and/or adherence to treatment (treatment adherence, treatment completion, SVR12) among people who inject drugs/people receiving opioid substitution therapy. Following the risk of bias (EPHPP) and quality of evidence assessment (GRADE), evidence to decision tables were produced and shared for critical review with an expert panel convened by ECDC and EMCDDA. The expert panel provided further considerations on the benefit, acceptability, and transferability of interventions. *** RESULTS: Fourteen studies (using DAA therapy as well as DAA plus interferon-based theory) met eligibility criteria and were included in the analysis. Integrated care with case management, peer support, psychological interventions, contingency management, and cooperation between health care providers improved engagement in and adherence to HCV care in most studies. However, the quality of evidence was predominantly low to moderate. *** CONCLUSIONS: Available evidence suggests that integrated, people-centered approaches may improve engagement throughout the continuum of HCV care among people who inject drugs. For progressing HCV elimination efforts, interventions should be implemented in colocation with harm reduction and counselling activities and in combination with additional services, including opioid substitution treatment, directly observed therapy, peer support and/or contingency management.