We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.