Food insecurity has a paramount negative impact on the overall nutritional and health status of people living with the human immune deficiency virus, hence leading to opportunistic infections, rapid disease progression, hospitalizations, poor treatment outcomes, and mortality, both are intertwined and worsen one another through a mixture of nutritional, mental health, and behavioral pathways that heighten vulnerability to, and worsen the severity of, each condition. Nevertheless, little is known about the magnitude of food insecurity and associated factors among adults on antiretroviral therapy in the current study area. This study aims to assess the magnitude of food insecurity and associated factors among Adults on Antiretroviral Treatment in Dessie referral hospital South Wollo Zone, Northcentral Ethiopia. An institution-based cross-sectional study was conducted among 407 selected adults living with Human Immune Virus receiving Anti-Retroviral treatment in Dessie referral hospital. Data was entered into Epi-data version 3.1 and exported to STATA version 16.0 for cleaning and analysis. Bivariable and multivariable binary logistic regression analysis was carried out to identify factors associated with the outcome variable. Odds ratio along with 95% confidence interval was estimated to measure the strength of the association and the level of statistical significance was declared at a p-value less than 0.05. This study revealed that the magnitude of food insecurity was 62.4% (95% CI: 57.6, 44 66.8]. CD4 count <350 [AOR = 3.51, 95% CI: 1.88, 6.52], average monthly household income ≤ 40 USD [AOR = 2.34, 95% CI: 1.42, 3.84], World Health Organization clinical stage III&IV [AOR = 2.85, 95% CI: 1.61, 5.04], not getting any support [AOR = 3.04, 95% CI: 1.45, 6.38] were factors significantly associated with food insecurity. Social protection interventions targeting patients with CD4 <350, monthly income less than 40 USD/month, World Health Organization clinical stage III &IV, and those patients with no support are crucial interventions for food security.