With the rapid advancement of spectrometers, the imaging range of the electromagnetic spectrum starts growing narrower. The reduction of electromagnetic wave energy received in a single wavelength range leads more complex noise into the generated hyperspectral image (HSI), thus causing a severe cripple in the accuracy of subsequent applications. The requirement for the HSI mixed denoising algorithm’s accuracy is further lifted. To address this challenge, in this letter, we propose a novel difference continuity-regularized nonlocal tensor subspace low-rank learning (named DNTSLR) method for HSI mixed denoising. Technically, the original high-dimensional HSI data was first projected into a low-dimensional subspace spanned by a spectral difference continuous basis instead of an orthogonal basis, so the data continuity of the restored HSI spectrum and tensor low-rankness was guaranteed. Then, a cube matching strategy was employed to stack the nonlocal tensor patches from the projected coefficient tensor, and a shrinkage algorithm was used to approximate the low-rank coefficient tensor. Eventually, the subspace low-rank learning algorithm was designed to alternately separate the noise tensor and restore the latent clean low-rank HSI tensor. Extensive experiments on multiple open datasets validate that the proposed method realizes the state-of-the-art denoising accuracy for HSI.