Protecting stalled DNA replication forks from degradation by promiscuous nucleases is essential to prevent genomic instability, a major driving force of tumorigenesis. Several proteins commonly associated with the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) have been implicated in the stabilization of stalled forks. Human CtIP, in conjunction with the MRE11 nuclease complex, plays an important role in HR by promoting DSB resection. Here, we report an unanticipated function for CtIP in protecting reversed forks from degradation. Unlike BRCA proteins, which defend nascent DNA strands from nucleolytic attack by MRE11, we find that CtIP protects perturbed forks from erroneous over-resection by DNA2. Finally, we uncover functionally synergistic effects between CtIP and BRCA1 in mitigating replication-stress-induced genomic instability. Collectively, our findings reveal a DSB-resection- and MRE11-independent role for CtIP in preserving fork integrity that contributes to the survival of BRCA1-deficient cells. Display omitted •CtIP protects reversed forks from nucleolytic degradation•CtIP prevents DNA2-dependent over-resection of nascent strands•CtIP nuclease mutants are defective in fork protection•CtIP-mediated fork protection synergizes with BRCA1, not BRCA2 Przetocka et al. identify a function of CtIP in maintaining replication fork stability that is distinct from its role in DSB resection. CtIP keeps DNA2 nuclease in check to limit the degradation of stalled forks. Loss of CtIP in BRCA1-deficient cells aggravates replication-stress-induced genomic instability, causing synthetic lethality.