Objective To estimate the absorption peak of methylene blue and its derivatives and construct a quantitative structure-activity relationship (QSAR) model for the absorption peak and structure. Methods Structure and absorption peak data of methylene blue and 17 derivatives were collected. The Waikato Environment for Knowledge Analysis (WEKA) method was used to normalize the data and conduct the modeling and prediction. Results The constructed fitting model was tested via cross validation and an external test set. The values of derived correlation coefficient R of the model from two tests were 0.8 and 0.9. Conclusion A QSAR model for the structure and absorption peak of methylene blue and its derivatives has been successfully constructed via WEKA method. This model can provide evidence for developing these compounds into photosensitizer and transforming structures for some potential compounds.