Invasive diseases is the diseases caused by bacterial infections that attack parts of the body such as bloodstream, soft tissue, and meninges. Invasive diseases are often associated with diseases such as pneumonia, meningitis, and sepsis. In Indonesia, pneumonia is the second leading caused of death in children. The incidence of meningitis in the worldwide reaches 1.2 million cases each year with patient’s mortality ranging from 2% -30%. Sepsis is a condition which is still a world health problem because of its difficult treatment and caused the rate of death is high enough. This study aims to determine the cost of illness in the treatment of invasive diseases in pediatric at PKU Muhammadiyah Yogyakarta Hospital. And to aims the comparison of direct medical cost with INA-CBG's cost based on Peraturan Menteri Kesehatan Republik Indonesia Nomor 64 Tahun 2016 in the treatment of invasive diseases in pediatrics at PKU Muhammadiyah Yogyakarta Hospital. The methods to answer the questions were used descriptive analysis and independent sample t-test. Based on the research that the cost of illness in the treatment of invasive diseases in pediatric at PKU Muhammadiyah Yogyakarta Hospital on pneumonia used the 3rd class of ward Rp2.804.012, the 2nd class of ward Rp3.320.765, the 1st class of ward Rp4.990.600, and meningitis used the 2nd class of ward Rp8.778.000. There were significant differences in the ratio of direct medical cost and INA-CBG's cost to the treatment of invasive diseases that have a primary diagnosis of pneumonia with the code of INA-CBG’s J-4-16-I used the 3rd class of ward and the diffrences Rp1.484.900 (p = 0,000). There were no significant differences in the ratio of direct medical cost and INA-CBG's cost to the treatment of invasive diseases that have a primary diagnosis of pneumonia with the code of INA-CBG’s J-4-16-I used the 2nd class of ward and the differences Rp861.325 (p = 0,322). There were significant differences in the ratio of direct medical cost and INA-CBG's cost to the treatment of invasive diseases that have the secondary diagnosis of pneumonia with the code of INA-CBG’s G-4-22-I used the 2nd class of ward and the differences Rp1.046.062 ( p = 0,033).