Abstract: The lead-bismuth fast reactor is one of the important types of fourth-generation reactors. It uses liquid lead-bismuth as the heat transfer medium, which has advantages such as inherent safety and ease of modularization. The wire-wrapped fuel rod is the core component in the lead-bismuth fast reactor, and exhibits complex flow induced vibration phenomena under the excitation of lead-bismuth, which can lead to fretting wear and damage of cladding. To quantitatively analyze the flow-induced vibration and fretting wear of a wire-wrapped fuel rod, understand the influences of typical parameters on the results of vibration response and fretting wear, and estimate the lifetime of cladding. Firstly, a nonlinear flow induced vibration theoretical model was established, considering the turbulent excitation, contact between wire and adjacent rod, and the nonlinear fluid-elastic force. Then, the flow-induced vibration experiment of the wire-wrapped fuel rod in lead-bismuth medium was used to obtain the strain results of the structure under typical flow velocity. The experimental results proved the applicability of the theoretical model. Finally, the laws of vibration displacement, strain, contact force and the maximal wear depth rate with the dimensionless flow velocity were obtained. The results show that the displacement and strain of the wire-wrapped fuel rod are positively correlated with the dimensionless flow velocity, and their probability density conforms to the Weibull distribution. For dimensionless flow velocity 0.2, the maximal dimensionless impact force and friction force root mean square values are 0.370 and 0.039, respectively. The maximal wear depth rate of cladding is logarithmically positively correlated with the dimensionless flow velocity. When the dimensionless flow velocity equals 0.2, the maximal wear depth rate can be 16.5 μm/year. The developed theoretical model for the nonlinear flow-induced vibration of wire-wrapped fuel rod provides an effective tool for quantitatively conducting vibration response and fretting wear analysis, and a basis for the mechanical design and evaluation of lead-bismuth fast reactor fuel assembly.