After analyzing quantitatively the sensitivity of sea surface emissivity, sea surface wind, sea water salinity, atmospheric transmittance, and atmospheric upwellward/downward radiation on the sea surface temperature (SST) retrieval from a single channel physical-based SST algorithm, it was concluded that that sea surface emissivity and atmospheric transmittance have greater impact on the accuracy of SST retrieval than the others. Deriving SST with different single infrared channel (3.7 μm), we found that the mid-infrared single channel physical-based SST algorithm is less sensitive to the accuracy requirements of these input parameters than that based in thermal band (11 μm and 12 μm). The night-time MODIS data taken in the Gulf of Mexico around the year of 2009 was used to validate the feasibility and accuracy of this algorithm and the sensitivity analysis. The result shows that the single physical channel method based on mid-infrared band is the optimal choice in case only one infrared channel is available on the space instrument. Furthermore, the algorithm at mid-infrared band can help to derive the operational coefficients for traditional split-window algorithm.