BackgroundTreatment plans for squamous cell carcinoma of the head and neck (SCCHN) are individually decided in tumor board meetings but some treatment decision-steps lack objective prognostic estimates. Our purpose was to explore the potential of radiomics for SCCHN therapy-specific survival prognostication and to increase the models’ interpretability by ranking the features based on their predictive importance.MethodsWe included 157 SCCHN patients (male, 119; female, 38; mean age, 64.39 ± 10.71 years) with baseline head and neck CT between 09/2014 and 08/2020 in this retrospective study. Patients were stratified according to their treatment. Using independent training and test datasets with cross-validation and 100 iterations, we identified, ranked and inter-correlated prognostic signatures using elastic net (EN) and random survival forest (RSF). We benchmarked the models against clinical parameters. Inter-reader variation was analyzed using intraclass-correlation coefficients (ICC).ResultsEN and RSF achieved top prognostication performances of AUC = 0.795 (95% CI 0.767–0.822) and AUC = 0.811 (95% CI 0.782–0.839). RSF prognostication slightly outperformed the EN for the complete (ΔAUC 0.035,p= 0.002) and radiochemotherapy (ΔAUC 0.092,p< 0.001) cohort. RSF was superior to most clinical benchmarking (p≤ 0.006). The inter-reader correlation was moderate or high for all features classes (ICC ≥ 0.77 (± 0.19)). Shape features had the highest prognostic importance, followed by texture features.ConclusionsEN and RSF built on radiomics features may be used for survival prognostication. The prognostically leading features may vary between treatment subgroups. This warrants further validation to potentially aid clinical treatment decision making in the future.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12880-023-01034-1.