PURPOSE: To investigate which demographic, personal, clinical, physical, psychological, social, lifestyle, and cancer-related quality of life (QoL) factors are associated with (changes in) supportive care needs (SCNs) from 6 months to 2 years after treatment in head and neck cancer (HNC) patients. METHODS: Data from the prospective NETherlands QUality of life and BIomedical Cohort (NET-QUBIC) study among HNC patients treated with curative intent was used. SCNs were measured using the Supportive Care Needs Survey 34-item Short-Form (SCNS-SF34) (6 months, 1 and 2 years after treatment) and the 11-item HNC-specific module (SCNS-HNC) (2 years). Multivariable linear mixed model analyses and linear regression analyses were used to study factors associated with changes in SCNs over time (SCNS-SF34) and the level of SCNs at 2 years follow-up (SCNS-SF34 and SCNS-HNC). RESULTS: Data from 483 patients was used. SCNs in the physical and daily living (PDL), psychological (PSY), and health system, information, and patient support (HSIPS) domains decreased significantly over time. At 2 years follow-up, the highest SCNs were reported regarding lack of energy/tiredness (10.8%). Changes in SCNs and the absolute level of SCNs at 2 years were associated with personal and clinical factors and post-treatment (6 months) with psychological, lifestyle, and cancer-related QoL factors. CONCLUSIONS: Personal, clinical, psychological, lifestyle, and cancer-related QoL factors were associated with SCNs. These results can be used to develop predictive models to personalize supportive care for HNC patients. IMPLICATIONS FOR CANCER SURVIVORS: SCNs decrease over time, but a subgroup of patients still presents with SCNs 2 years after treatment.