Objective This database analysis was performed to analyze the expression and clinical significance of Ras protein activator like 1 (RASAL1) and Ras protein activator like 2 (RASAL2) in non-small cell lung cancer (NSCLC). Methods Using Oncomine, we comprehensively compared the differential expression of RASAL1 and RASAL2 genes in NSCLC and normal lung tissues. The relationship between the expressions of RASAL1 and RASAL2 and the prognosis of NSCLC was retrieved from the Kaplan-Meier plotter database. Results In the Oncomine data analysis, RASAL1 was increased and RASAL2 was decreased in NSCLC ( P <0. 05 for both). The Kaplan-Meier plotter data analysis indicated that low expression of RASAL1 and high expression of RASAL2 were closely associated with a good prognosis, including overall survival and post-progression survival. Furthermore, low expression of RASAL1 was associated with a good prognosis in patients with NSCLC receiving chemotherapy and radiotherapy. Conclusions In NSCLC, RASAL1 is increased and RASAL2 is decreased, and they are associated with patients’ clinical prognosis. RASAL1 may promote and RASAL2 may suppress the development of NSCLC. The effect of RASAL1 on the prognosis of patients with NSCLC is also related to radiotherapy and chemotherapy, and RASAL1 may thus be a potential therapeutic target for NSCLC.