In hyperspectral image processing, anomaly detection is a valuable way of searching targets whose spectral characteristics are not known, and the estimation of background signals is the key procedure. On account of the high dimensionality and complexity of hyperspectral image, dimensionality reduction and background suppression is necessary. In addition, the complementarity of different anomaly detection algorithms can be utilized to improve the effectiveness of anomaly detection. In this paper, we propose a novel method of anomaly detection, which is based on clustering of optimized K-means and decision-level fusion. In our proposed method, pixels with similar features are firstly clustered using an optimized k-means method. Secondly, dimensionality reduction is conducted using principle component analysis to reduce the amount of calculation. Then, to increase the accuracy of detection and decrease the false-alarm ratio, both Reed-Xiaoli (RX) and Kernel RX algorithm are used on processed image. Lastly, a decision-level fusion is processed on the detection results. A simulated hyperspectral image and a real hyperspectral one are both used to evaluate the performance of our proposed method. Visual analysis and quantative analysis of receiver operating characteristic (ROC) curves show that our algorithm can achieve better performance when compared with other classic approaches and state-of-the-art approaches.