Objective: Cancer survivors experience reduced overall health-related quality of life (HRQoL) compared to the general population. This research assesses and compares the efficacy of an emotion-focused (CanCopeMind [CM]) and lifestyle (CanCopeLifestyle [CL]) intervention to improve HRQoL among cancer survivors. Method: This 8-week, internet-delivered, randomized controlled trial compared CM (n = 110) and CL (n = 114) on self-reported HRQoL (range -0.022 = indicating a state akin to dead to 1.0 representing perfect health) at baseline, postintervention, and 3-month follow-up. CM, adapted from the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders, targeted core emotion regulation skills (understanding emotions, mindfulness, flexible thinking, and changing behaviors). CL, the active control, targeted healthy lifestyle domains (diet, exercise, relaxation, and sleep). Results: HRQoL increased in both groups from baseline to postintervention (CM, p < .001, SMDmedian = 0.54; CL, p < .001, SMDmedian = 0.40), and these improvements were sustained at follow-up (CM, p < .001, SMDmedian = 0.52; CL, p = .005, SMDmedian = 0.33). The difference between each group was not significant at either postintervention (p = .095, SMDmedian = 0.19) or follow-up (p = .081, SMDmedian = 0.23). Subgroup analyses revealed no moderation by cancer stage, treatment type, months since treatment, cancer type or sex. Conclusion: The findings indicate that an accessible, internet-delivered emotion-focused and lifestyle interventions hold promise for improving HRQoL among cancer survivors.