HSIs (hyperspectral images) obtained by new-generation hyperspectral sensors contain both electronic noise and photon noise with comparable power. Therefore, both the SI (signal-independent) component and the SD (signal-dependent) component have to be considered. In this paper, a superpixel-based noise estimation algorithm using MLR (multiple linear regression) is proposed for the above mixed noise to estimate the noise standard deviation of both SI component and SD component. First, superpixel segmentation is performed on the first principal component obtained by MNF (minimum noise fraction)-based dimensionality reduction to generate non-overlapping regions with similar pixels. Then, MLR is performed to remove the spectral correlation, and a system of linear equations with respect to noise variances is established according to the local sample statistics calculated within each superpixel. By solving the equations in terms of the least-squares method, the noise variances are determined. The experimental results show that the proposed algorithm provides more accurate local sample statistics, and yields a more accurate noise estimation than the other state-of-the-art algorithms for simulated HSIs. The results of the real-life data also verify the effectiveness of the proposed algorithm.