The invention discloses a method for rapidly predicting heterosis based on genome size, and belongs to the technical field of crop breeding. The method includes the following steps: S1. selecting a hybrid combination parent according to the relative difference percentage of genome size and Nei genetic distance between crops; S2. emasculating and hybridizing the selected hybrid combination parent to obtain F1 generation; S3. carrying out heterosis analysis on target traits of the F1 generation; S4. analyzing the correlation between heterosis of the target traits of the F1 generation and Nei genetic distance between parents; S5. analyzing the correlation between heterosis of the target traits of the F1 generation and absolute value of genome size difference between parents; and S6. combiningthe above analysis results, selecting strong heterosis hybrid combinations and predicting heterosis of the F1 generation at the same time. The breeding method is beneficial to improving breeding efficiency and reducing breeding cost, and has the advantage of wide applicability.