Background: Streptococcus pneumoniae is a gram-positive bacterium that causes various types of respiratory diseases such as pneumoniae, sinusitis, otitis, bronchitis and meningitis. Amoxicillin is a class of penicillin β-lactam antibiotic which works to inhibit cell wall synthesis of gram-positive bacteria such as Streptococcus pneumoniae. Lysozyme is an enzyme that has a role in killing gram-positive bacteria by lyses the peptidoglycan cell wall. Research Aims: To determine the effectiveness of lysozyme in reducing Amoxicillin minimal inhibitory levels against the bacteria Streptococcus pneumoniae. Research Method: This research is experimental laboratory. Materials used include: Local Streptococcus pneumoniae strains, Amoxicillin, lysozyme (sigma), Tryptone Soya Agar (TSA) and Brain Heart Infusion (BHI) media. Determination of the combination of minimal lysozyme and Amoxicillin combination with a liquid dilution series method (tube dilution series). Research Results: Based on the KHM examination with the dilution method, the following results are obtained: KHM lysozyme against Streptococcus pneumonia > 300 μg / ml, MIC Amoxicillin against Streptoccus pneumoniae 166.67 μg / ml, and a combination of lysozyme and Amoxicillin against Streptoccus pneumoniae 12,34 μg / ml. The results of data analysis using Oney Way Anova were obtained p <0.05 for MIC combination of lysozyme and Amoxicillin. This proves that the addition of lysozyme can reduce the rate of MIC in Amoxicillin against Amoxicillin-resistant Streptococcus pneumoniae. Conclusion: Lysozyme with levels of 300 μg / ml does not have an antibacterial effect on Amoxicillin-resistant Streptococcus pneumoniae. The combination of lysozyme and Amoxicillin was able to reduce Amoxicillin minimal inhibitory concentration against Amoxicillin-resistant Streptococcus pneumoniae.