Objective: Under the DIP payment schemes, all anti-tumor drugs are paid using the same payment standard, which is insufficient to reasonably reflect the value of various drugs. Using lung cancer drugs as an example, this study examined the cost differences of anti-tumor drugs based on drug mechanisms and innovation levels, and explored the methodology for adjusting the payment standards for DIP cancer diseases. Methods: Lung cancer patients admitted to two tertiary hospitals in Guangzhou from 2018 to 2020 were selected. The costs of different types of drugs were analyzed and the four treatment groups were compared pairwise. We divided the treatment groups with statistical differences in hospitalization expenses and a percentage difference greater than the given threshold into different disease groups for payment, and compared the impact of subdivision on the medical insurance fund budget. Results: The average hospitalization cost for the immunotherapy combined with chemotherapy group, the mono-immunotherapy group, the mono-targeted therapy group and the mono-chemotherapy group were 26379 yuan, 18832 yuan, 16345 yuan, 13753 yuan per case, respectively. There were statistical differences in the total hospitalization expenses among the four treatment groups, and the percentage difference was 20% higher than the base group. The budget impact analysis indicated further segmentation of disease groups could lead to overall decrease or stability of medical insurance funds due to reduction in expenses associated with a large amount of unnecessary chemotherapy. Conclusion: Dynamic adjustment of payment standard based on real world data could support refined management of medical insurance, increase hospital access of innovative negotiated drugs, and promote clinical rational drug use.