Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, a definitive diagnosis of cSCC is crucial to prevent patients from missing out on treatment. The gold standard for the diagnosis of cSCC is still pathological biopsy. Currently, its diagnostic efficiency and accuracy largely depend on the experience of pathologists. Here, we present a simple, fast, and robust technique, a microscopic multispectral imaging system based on LED illumination, to diagnose cSCC qualitatively and quantitatively. The adaptive threshold segmentation method was used to segment the multispectral images into characteristic structures. There was a statistically significant difference between the average nucleocytoplasmic ratio of normal skin (4.239%) and cSCC tissues (15.607%) (p < 0.01), and the keratin pearls cSCC have well-defined qualitative features. These results show that the qualitative and quantitative features obtained from multispectral imaging can be used to comprehensively determine whether or not the tissue is cancerous. This work has significant implications for the development of a low-cost and easy-to-use device, which can not only reduce the complexity of pathological diagnosis but can also achieve the goal of convenient digital staining and access to critical histological information.