Background: Food insecurity disproportionately impacts immigrant, low-income, and racial and ethnic minorities with cancer. In our prior qualitative work, Latinx and multiethnic patients with food insecurity emphasized the importance of culturally-tailored food assistance interventions that could minimize stigma and maintain self-efficacy and autonomy. In collaboration with Latinx patients and community partners in Monterey County, California, we co-developed a culturally-tailored food voucher intervention. In this study, we conducted a pilot of the intervention among multiethnic and Latinx patients with cancer and tested the impact on food insecurity and health-related quality of life. Methods: We recruited low-income, racial and ethnic minority adults > 18 years of age who screened positive for food insecurity using the 2-item Hunger Vital Sign while receiving cancer treatment in a clinic in Monterey County, CA between July 2023 until August 2023. All participants who consented to participate received $40 monthly grocery store gift cards redeemable at a variety of local retailers for 6 months in addition to usual care provided by trained community health workers who assisted with other health-related social needs. We conducted validated surveys at baseline (time of enrollment) and 6-month follow-up (post-intervention) assessing demographics, food behaviors, food insecurity, and health-related quality of life, as well as feasibility and acceptability of the intervention. We compared pre- and post-intervention proportions with food insecurity using McNemars tests and change in health-related quality of life using paired t-tests. Results: Of the 30 study participants enrolled, 27 (90%) were Latinx; 24 (80%) spoke Spanish as their preferred language; 16 (53%) had advanced (stage 3 or 4) cancer; 12 (40%) were retired or unemployed; 10 (33%) were disabled; 20 (67%) reported a household income < $35,000 USD. Of the 26 (87%) participants who completed post-intervention surveys, the proportion with food insecurity decreased from 100% to 65% (95% CI 0.60-0.77; p = 0.01); 100% adhered to recommended treatment; and health-related quality of life scores increased by 8 points from 71.9 +/-16.1 to 79.5+/- 10.5 (p = 0.02) from baseline. All (100%) participants rated the program as feasible and acceptable in post-intervention surveys. Conclusions: This culturally-tailored food voucher intervention was associated with reductions in food insecurity and improvements in health-related quality of life among low-income Latinx patients with cancer. This intervention may represent an effective and acceptable approach to overcome food insecurity in Latinx and multiethnic patients with cancer.