The study examined knowledge, attitudes and practices (KAP) about adverse reactions to chemotherapy and care in patients with gastrointestinal lymphoma. A cross-sectional study was conducted from March to May 2024 at Peking University Inner Mongolia Cancer Hospital, China, with 422 patients. The mean scores for knowledge were 12.93 ± 4.21 (range 0–22), attitudes 27.57 ± 3.72 (range 7–35), and practices 33.57 ± 3.19 (range 8–40). Regression analysis showed that higher knowledge scores significantly affect attitudes (OR = 1.397, P < 0.001) and practices (OR = 1.235, P < 0.001). Structural equation analysis (SEM) confirmed a direct effect of knowledge on practices (β = 0.161, P < 0.001) and an indirect effect through attitudes (β = 0.649, P < 0.001). Patients demonstrated moderate knowledge, positive attitudes, and good practices. Targeted interventions to improve knowledge are particularly recommended for rural patients and those with lower incomes.