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A flat-field correction method is proposed for multiple measured hyperspectral microscopy imaging in this paper. As the most crucial preprocessing process in quantitative microscopic analysis, flat-field correction solves the uneven illumination caused by vignetting in microscopic images, and guarantees the precision of spatial and spectral information in hyperspectral microscopic imaging. In order to carry out flat-field correction and extract uneven illumination among groups of hyperspectral microscopic data containing hundreds of bands simultaneously, two properties of vignetting have been exploited: i) low-rank property is reflected by little information contained in vignetting; ii) local smoothness can be observed as a gradual change in brightness of vignetting, which is typically equivalent to the sparseness in spatial frequency domain. Combining the two properties above, a novel Low Rank Smooth Flat-field Correction (LRSFC) model modified from common orthogonal basis extraction is proposed, while an optimization is solved based on alternating direction multiplier method (ADMM), obtaining a unique flat-field term with low-rank and smooth properties. Qualitative and quantitative experimental assessments indicate that LRSFC does not add extra cell texture to the extracted flat-field term, whose performance appears prior to other state-of-the-art flat-field correction methods. [ABSTRACT FROM AUTHOR]