Oral squamous cell carcinoma (OSCC) is the most fatal cancer and has poor survival rate among all cancers. Regular screening of patients can reduce fatality rate of OSCC. Usually, oral cancer screening is accomplished by visual examinations and conventional endoscopes. These regular conventional endoscopes are not able to provide microstructure of altered OSCC tissue so use of micro-endoscopes are favorable for cancer screening, since it can give morphology of altered OSCC tissue. Similarly, the fluorescence (FL) spectroscopy of OSCC tissue can probe the molecular levels of tissue giving information about the progression of oral cancer as it is biophysical and biochemical sensitive. The motivation behind this study is to analyze OSCC by simultaneous micro-endoscopy and spectroscopy with the help of in-house-fabricated low-cost micro-endoscopic system. Simultaneous FL imaging with spectroscopy can provide the morphological changes in altered tissue and record the corresponding intensity counts, wavelength shift and area under the curve (AUC) of the sample. These spectroscopic parameters are directly linked with molecular transitions within the tissue and can be used in real-time cancer screening. FL micro-endoscopic images gives information about fluorescence contrast distribution within the tissue and differ in mean intensity, skewness, kurtosis and energy for OSCC and normal tissue. Present study included 10 OSCC patients and 8 control patients. The value of mean intensity, skewness, kurtosis, energy, peak wavelength, AUC and max counts for OSCC is 163.3±30, -0.567±0.33, 7.82±5.2, ~4.24×105 , 533.28±1.73, ~4.5×106 , ~4.05×104 , respectively and for normal tissue is 63.5±22.4, 0.148±0.05, 4.89±3.89, ~1.65×105 , 528.89±0.81, ~3.3×106 , ~4.63×103 , respectively. The observations from the present study are in-line with screening requirements of OSCC in regular basis screening and suitable for low-resource setting area.