Electronic patient portals represent a promising means of integrating mental health assessments into HIV care where anxiety and depression are highly prevalent. Patient attitudes toward portal-based mental health screening within HIV clinics have not been well described. The aim of this formative qualitative study is to characterize the patient-perceived facilitators and barriers to portal-based anxiety and depression screening within HIV care in order to inform implementation strategies for mental health screening. Twelve adult HIV clinic patients participated in semi-structured interviews that were audio recorded and transcribed. The transcripts were coded using constructs from the Consolidated Framework for Implementation Research and analyzed thematically to identify the barriers to and facilitators of portal-based anxiety and depression screening. Facilitators included an absence of alternative screening methods, an approachable design, perceived adaptability, high compatibility with HIV care, the potential for linkage to treatment, an increased self-awareness of mental health conditions, the ability to bundle screening with clinic visits, and communicating an action plan for results. The barriers included difficulty navigating the patient portal system, a lack of technical support, stigmatization from the healthcare system, care team response times, and the novelty of using patient portals for communication. The patients in the HIV clinic viewed the use of a portal-based anxiety and depression screening tool as highly compatible with routine HIV care. Technical difficulties, follow-up concerns, and a fear of stigmatization were commonly perceived as barriers to portal use. The results of this study can be used to inform implementation strategies when designing or incorporating portal-based mental health screening into other HIV care settings.