Cisplatin resistance is frequently occurred in ovarian cancer therapy, understanding its regulatory mechanisms is critical for developing novel treatment methods and drugs. Here, we found ovarian cancer patients with low FAM83B levels had shorter survival time, tissues with cisplatin resistance also had low FAM83B levels, suggesting FAM83B might inhibit cisplatin resistance. FAM83B overexpression inhibits cisplatin resistance showed in increased ovarian cancer cell proliferation and growth rate, and reduced apoptosis rate, while FAM83B knockdown promotes cisplatin resistance. Mechanism analysis showed FAM83B interacted with APC to inhibit Wnt pathway activity, causing ovarian cancer cisplatin resistance. We also found FAM83B levels were negative with Wnt pathway activity in clinic samples, confirming FAM83B inhibited Wnt pathway activity. In summary, we found FAM83B inhibits ovarian cancer cisplatin resistance through inhibiting Wnt pathway, providing a new target for ovarian cancer therapy.