Background Lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) adolescents and young adults (AYAs) report higher levels of distress than non-LGBTQI AYAs with cancer, and LGBTQI adults with cancer. This mixed methods study examined LGBTQI AYA’s experiences of cancer and cancer care, to understand this distress.Methods Online surveys were completed by 95 LGBTQI AYAs (age 16–39 years); 19 AYAs took part in a one-to-one semi structured interview. Reflexive thematic analysis of interviews and open-ended survey responses facilitated in-depth examination of subjective experiences; descriptive statistics performed on closed-ended survey items identified the percentage of AYAs reporting experiences identified in the qualitative analysis.Results 63% of AYAs reported high or very high distress. Three themes identified in the qualitative analysis included: 1) “Identities in flux”, included subthemes “Cancer disrupts developing identities, and involvement with LGBTQI communities”; “Internalized prejudice impacts identities”; and “Cancer facilitates identities and embodiment”. 2) “Invisibility in cancer care”, included subthemes “Navigating disclosure amongst cis-heteronormative assumptions”, “Discrimination and paternalistic cancer care” and “Cis-heteronormativity within cancer information”. 3) “Precarious social support for LGBTQI AYAs with cancer”, included subthemes “Social support during cancer is helpful for LGBTQI AYAs”, “LGBTQI AYAs navigate limited support”, and “Finding cancer peer support networks is difficult for LGBTQI AYAs”.Conclusions LGBTQI AYAs with cancer experience psychosocial vulnerabilities related to identity development, experiences of care, and social support networks. These factors likely contribute to their previously evidenced elevated risk of distress, relative to both non-LBGTQI AYAs and LGBTQI older adults. AYAs affected by cancer may require additional, tailored supportive care, including targeted information resources, LGBTQI AYA specific cancer support groups, or partnerships and referrals to LGBTQI community organisations. Additionally, it is evident that health care professionals and cancer services have much work to do in ensuring LGBTQI AYAs receive affirming and appropriate care across paediatric and adult clinical settings. They must move beyond assuming all patients are cisgender, heterosexual and do not have intersex variations unless otherwise stated; work to signal inclusivity and facilitate disclosure; and be able to respond appropriately with tailored information and care, which is inclusive of LGBTQI partners, chosen family, and support systems.