As one of the most important brain-computer interface (BCI) paradigms, P300-Speller was shown to be significantly impaired once applied in practical situations due to effects of mental workload. This study aims to provide a new method of building training models to enhance performance of P300-Speller under mental workload. Three experiment conditions based on row-column P300-Speller paradigm were performed including speller-only, 3-back-speller and mental-arithmetic-speller. Data under dual-task conditions were introduced to speller-only data respectively to build new training models. Then performance of classifiers with different models was compared under the same testing condition. The results showed that when tasks of imported training data and testing data were the same, character recognition accuracies and round accuracies of P300-Speller with mixed-data training models significantly improved (FDR, p < 0.005). When they were different, performance significantly improved when tested on mental-arithmetic-speller (FDR, p < 0.05) while the improvement was modest when tested on n-back-speller (FDR, p < 0.1). The analysis of ERPs revealed that ERP difference between training data and testing data was significantly diminished when the dual-task data was introduced to training data (FDR, p < 0.05). The new method of training classifier on mixed data proved to be effective in enhancing performance of P300-Speller under mental workload, confirmed the feasibility to build a universal training model and overcome the effects of mental workload in its practical applications.