For patients and their intimate partners, advanced cancer poses significant physical and emotional challenges that can negatively impact both the individuals and the couple. Couples’ ability to communicate openly and effectively with each other about cancer-related concerns can improve their psychological adjustment and the quality of their relationship. It may also lead to better symptom management and goal-concordant care for the patient. However, many couples report difficulties communicating about cancer, even in the context of overall satisfying relationships. Prior research has found that couple-based interventions that target communication lead to positive outcomes for cancer patients and their partners. However, most have been limited by an in-person treatment delivery format that precludes many couples from participating; they have also not targeted interventions to couples most at risk for poor outcomes. To address these limitations, this study will conduct an RCT to test the efficacy of a Couples Communication Skills Training (CCST) intervention delivered via videoconference for couples facing advanced cancer. The intervention is targeted to couples who report high levels of holding back from discussing cancer-related concerns, a variable associated with poorer psychological and relationship functioning. The CCST intervention includes components to assist couples communicate effectively, decrease avoidance of important cancer-related issues, and provide each other with support. In this study, 230 patients with advanced GI, GU, breast, or lung cancer and their partners will be randomly assigned to one of two conditions: 1) CCST, or 2) Education. All participants will be provided with tablet computers with internet access for videoconferencing. Assessments, including self-report measures and audio recorded couple conversations, will be conducted with patients and partners at baseline, mid-treatment, and posttreatment. Self-report measures will also be collected at 3 months follow up. The primary hypothesis to be tested is that patients and partners in the CCST intervention will report significantly higher levels of relationship satisfaction and intimacy relative to those in the education condition. Secondary aims will focus on (a) improvements in patient and partner psychological adjustment; (b) improvements in patient health and health care outcomes; and (c) whether improvements in individual and relationship functioning are mediated by improvements in self-reported and objective measures of communication. Exploratory analyses include (a) examination of moderators of intervention effects, and (b) an implementation-related process evaluation of the intervention guided by the RE-AIM framework to expedite translation of the intervention into clinical practice.