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Unevenness is one of the important parameters for evaluating yarn quality, but the current prediction accuracy of yarn unevenness is low. One of the important reasons is that there are few sample dataset for yarn unevenness prediction. For this problem, this paper applies generalized regression neural network to predict the unevenness of the yarn. Then, the generalized regression neural network is optimized by using particle swarm optimization, fruit fly optimization algorithm, and gray wolf optimizer, respectively. Finally, the optimized models were experimentally validated for their effectiveness. The experimental results show that the generalized regression neural network optimized by gray wolf optimizer has the best effect and the fastest optimization speed; the generalized regression neural network optimized by particle swarm optimization algorithm has the middle optimization speed; the generalized regression neural network optimized by fruit fly optimization algorithm has the worst effect and the slowest optimization speed.