This study aimed to investigate the extent to which variables directly related to science, which are found in the Programme for International Student Assessment (PISA) 2015 survey predicted the science literacy performance of students in Turkey and Singapore samples and determine the differences and similarities between the samples of the two countries. The study used the relational screening model. The study sample consisted of a total of 9680 students at the age of 15, which included 4643 students from the Turkey sample and 5037 students from the Singapore sample. Also, the sample included 177 schools from Turkey and 163 schools from Singapore. The study used the Hierarchical Linear Modeling (HLM) statistical technique, which is appropriate for hierarchical data because the school and student-level variables were together in the study. According to the findings of the study, science literacy performance indicated a significant difference between schools for both countries. However, approximately 52% of the difference in students' science literacy scores for Turkey sample and 34% for Singapore sample were found to stem from differences between schools. Student-level interest in science, research-based science teaching and learning practices, teacher support in science lessons, science self-efficacy, teacher-centered science teaching variables, and the proportion of science teachers at school level were determined to be a significant predictor of science literacy in both countries. However, the variables which are the significant predictors of science literacy were found to be “the enjoyment of science” for Turkey and “the disciplinary climate in science courses” variable for Singapore. On the other hand, the proportion of science teachers with an undergraduate education of four years or more, which is one of the school-level variables, was found to be not a significant predictor of science literacy performance for both countries.