Flow chart of RFMSE. Display omitted •We propose a misclassification synthetic minority over-sampling technique, which overcomes the blindness of the synthetic minority over-sampling technique in synthesizing samples.•Our sampling algorithm optimally integrates the advantages of data resampling algorithm and random forest algorithm.•Our sampling algorithm uses the misclassification synthetic minority over-sampling technique and the edited nearest neighbor under-sampling technique to sample the imbalanced data.•Extensive experiments show that our sampling algorithm better than other data resampling algorithm in medical diagnosis. The problem of imbalanced data classification often exists in medical diagnosis. Traditional classification algorithms usually assume that the number of samples in each class is similar and their misclassification cost during training is equal. However, the misclassification cost of patient samples is higher than that of healthy person samples. Therefore, how to increase the identification of patients without affecting the classification of healthy individuals is an urgent problem. In order to solve the problem of imbalanced data classification in medical diagnosis, we propose a hybrid sampling algorithm called RFMSE, which combines the Misclassification-oriented Synthetic minority over-sampling technique (M-SMOTE) and Edited nearset neighbor (ENN) based on Random forest (RF). The algorithm is mainly composed of three parts. First, M-SMOTE is used to increase the number of samples in the minority class, while the over-sampling rate of M-SMOTE is the misclassification rate of RF. Then, ENN is used to remove the noise ones from the majority samples. Finally, RF is used to perform classification prediction for the samples after hybrid sampling, and the stopping criterion for iterations is determined according to the changes of the classification index (i.e. Matthews Correlation Coefficient (MCC)). When the value of MCC continuously drops, the process of iterations will be stopped. Extensive experiments conducted on ten UCI datasets demonstrate that RFMSE can effectively solve the problem of imbalanced data classification. Compared with traditional algorithms, our method can improve F-value and MCC more effectively.