This study examined the association of needs, health literacy, and quality of life among adult Nigerians with cancer and family caregivers. A descriptive study was conducted involving 240 adults with cancer and family caregivers attending a tertiary hospital. More than two-thirds of participants reported moderate or high needs. Information (90.8%) and spiritual support (85%) were the domains of highest need among adults with cancer. Family/social support (85%) and spiritual support (81.7%) ranked the highest among family caregivers. A negative correlation was found between needs and quality of life. Stepwise regression analysis showed that needs and literacy explained 36% of the variance in adults with cancer's quality of life and 28% of the variance in family caregivers’ quality of life. Spiritual need accounted l for 9.5% and 9.1% of variation for adults with cancer and family caregivers, respectively. Findings suggest that interventions with a focus on social/family and spiritual needs may improve wellbeing of adults with cancer and caregivers in Nigeria. This research are generalizable to other low-income countries where family values and spirituality are often a strong feature of daily life.