Thermal therapy, destroying tumor in situ by localized heating, is emerging as one of the treatment options for benign and localized tumors. Despite many advantages of thermal therapy, its clinical application is still limited due to the lack of a reliable intraoperative monitoring technique of the thermal lesion. To address this challenge, an intraoperative thermometry technique has been proposed using the temperature-dependent fluorescence of quantum dots (QDs). Its feasibility is recently demonstrated by monitoring the spatiotemporal temperature during gold nanoshell-mediated heating. In the present study, the effects of tissue-light interaction on the QD-mediated thermometry were investigated both experimentally and theoretically so that the technique can be extended to in vivo applications. As for experimental investigation, the QD fluorescence through tissue phantom was characterized with varying the thickness of the phantom over a temperature range relevant to thermal therapy. The results showed that the QD fluorescence through tissue phantom was still linearly correlated to the local temperature, but the slope of the correlations decreased with the phantom thickness. As for theoretical investigation, the radiative transfer equation was reduced to the diffusion approximation, and the QD fluorescence through tissue phantom was predicted by numerically solving the diffusion approximation. The results confirmed that the diffusion approximation could describe the tissue-light interaction for the QD-mediated thermometry but further research is still required to improve the accuracy of the prediction.