A system for predicting therapy resistance and its molecular mechanisms in rectal cancer before treatment is provided. The system includes a feature extraction device, a collection device, a signature construction device and a prediction device. The system can predict responses to neoadjuvant therapy in patients before treatment, analyze patients who are resistant to rectal cancer therapy and their underlying molecular mechanism, thereby enabling personalized therapy for patients who are resistant to rectal cancer therapy. The system has important clinical significance in improving the overall survival of rectal cancer patients.