We evaluated whether fluorescence intensity (FI) and its coefficient of variation (CV) can be used to diagnose squamous cell carcinoma (SCC) through IllumiScan^®, an oral mucosa fluorescence visualisation (FV) device. Overall, 190 patients with oral mucosal lesions (OMLs; SCC, 59; non-SCC OMLs, 131) and 49 patients with normal oral mucosa (NOM) were enrolled between January 2019 and March 2021. The FI of the images was analysed using image analysis software. After establishing regions of interest for SCC, non-SCC, and NOM, the average FI, standard deviation (SD), and CV were compared. There was a significant difference in the average FI for all pairs of comparisons. The SD was not significantly different between the SCC and NOM groups (p = 0.07). The CV differed significantly for NOM (p < 0.001) and non-SCC groups (p < 0.001) relative to the SCC group but was not different between NOM and non-SCC groups (p = 0.15). Univariate analysis of SCC and non-SCC groups showed significant differences for all factors, except age. However, multivariate analysis showed a significant intergroup difference only in the CV (p = 0.038). Therefore, analysing the CV in FV images of OML may be useful for the diagnosis of oral cancer.