Background: Cancer is one of the common diseases in childhood, the diagnosis of which shocks parents, especially mothers. Meanwhile, parents' adaptation to the disease reduces complications and problems. Objectives: Therefore, this study was aimed at exploring the impact of Roy adaptation model on care burden in mothers of children under chemotherapy. Methods: This quasi-experimental study was performed on 36 mothers of children under chemotherapy who had referred to the oncology ward of Taleghani Hospital, Gorgan, in 2018. Random sampling was carried out for both control and experimental groups. The experimental group received a training program based on Roy adaptation model during seven sessions over a four-week period. Data were collected using the Caregiver's Burden Scale (CBS) devised by Elmstahl. The results were analyzed in SPSS-18 using independent and paired t tests as well as covariance test at the significance level of P < 0.05. Results: The means of care burden before the intervention in the experimental and control groups were respectively 70.44 ± 7.04 and 67.11 ± 6.54. The independent t test did not reveal any significant difference in this regard (P = 0.15). However, after the intervention, the mean of care burden significantly differed between the experimental (50.94 ± 4.58) and control (70.88 ± 5.13) groups, as confirmed by independent t test (P < 0.001). Conclusions: Based on the results, deploying the care program based on Roy adaptation model is an effective, low-cost, and noninvasive nursing intervention for mothers of children with cancer.