Thyroid hormone receptor interactor 13 (TRIP13) plays a crucial role in poor prognosis and chemotherapy resistance of cancer patients. This present study is aimed at investigating the role of high expression of TRIP13 inducing nedaplatin (NDP) resistance in esophageal squamous cell carcinoma (ESCC) cells. High expression of TRIP13 promoted the proliferation and migration of ESCC cells performed by MTS assay, colony formation assay, wound healing assay, and transwell assay. High TRIP13 expression induced NDP resistance to ESCC based on the cell proliferation promoting/inhibition rate and cell migration promoting/inhibition rate analysis, flow cytometry assay of apoptotic subpopulations with a combination of Annexin V-FITC and propidium iodide, and Western blot analysis downregulating cleaved PARP, γH2A.X, cleaved caspase-3, and Bax and upregulating Bcl-2 expression. This study indicated that high expression of TRIP13 promoted proliferation and migration of ESCC cells and induced NDP resistance via enhancing repair of DNA damage and inhibiting apoptosis. This will provide a preliminary reference for the clinical use of NDP in ESCC treatment.