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BACKGROUND: Hepatitis B Virus (HBV) reactivation is the most common complication for patients with primary liver cancer (PLC) after radiotherapy. How to reduce the reactivation of HBV has been a hot topic in the study of postoperative radiotherapy for liver cancer. OBJECTIVE: To find out the inducement of HBV reactivation, a feature selection algorithm (MIC-CS) using maximum information coefficient (MIC) combined with cosine similarity (CS) was proposed to screen the risk factors that may affect HBV reactivation. METHOD: Firstly, different factors were coded and MIC between patients was calculated to acquire the association between different factors and HBV reactivation. Secondly, a cosine similarity algorithm was constructed to calculate the similarity relationship between different factors, thus removing redundant information. Finally, combined with the weight of the two, the potential risk factors were sorted and the key factors leading to HBV reactivation were selected. RESULTS: The results indicated that HBV baseline, external boundary, TNM, KPS score, VD, AFP, and Child-Pugh could lead to HBV reactivation after radiotherapy. The classification model was constructed for the above factors, with the highest classification accuracy of 84% and the AUC value of 0.71. CONCLUSION: Comparing multiple feature selection methods, the results showed that the effect of the MIC-CS was significantly better than MIM, CMIM, and mRMR, so it has a very broad application prospect. [ABSTRACT FROM AUTHOR]