Purpose Deep Learning-based Radiomics (DLR) has achieved great success on medical image analysis. In this study, we aimed to explore the capability of our proposed end-to-end multi-modality DLR model using pretreatment PET/CT images to predict 5-year Progression-Free Survival (PFS) in advanced NPC.Methods A total of 170 patients with pathological confirmed advanced NPC (TNM stage III or IVa) were enrolled in this study. A 3D Convolutional Neural Network (CNN), with two branches to process PET and CT separately, was optimized to extract deep features from pretreatment multi-modality PET/CT images and use the derived features to predict the probability of 5-year PFS. Optionally, TNM stage, as a high-level clinical feature, can be integrated into our DLR model to further improve prognostic performance. Results For a comparison between Conventional Radiomic (CR) and DLR, 1456 handcrafted features were extracted, and three top CR methods, Random Forest (RF) + RF (AUC = 0.796 ± 0.009, testing error = 0.267 ± 0.007), RF + Adaptive Boosting (AdaBoost) (AUC = 0.783 ± 0.011, testing error = 0.286 ± 0.009), and L1-Logistic Regression (L1-LOG) + Kernel Support Vector Machines (KSVM) (AUC = 0.769 ± 0.008, testing error = 0.298 ± 0.006), were selected as benchmarks from 54 combinations of 6 feature selection methods and 9 classification methods. Compared to the three CR methods, our multi-modality DLR models using both PET and CT, with or without TNM stage (named PCT or PC model), resulted in the highest prognostic performance (PCT model: AUC = 0.842 ± 0.034, testing error = 0.194 ± 0.029; PC model: AUC = 0.825 ± 0.041, testing error = 0.223 ± 0.035). Furthermore, the multi-modality PCT model outperformed single-modality DLR models using only PET and TNM stage (named PT model: AUC = 0.818 ± 0.029, testing error = 0.218 ± 0.024) or only CT and TNM stage (named CT model: AUC = 0.657 ± 0.055, testing error = 0.375 ± 0.048). Conclusion Our study identified potential radiomics-based prognostic model for survival prediction in advanced NPC, and suggests that DLR could serve as a tool for aiding in cancer management.