With advances in imaging technology and surgical instruments, hepatectomy can be perfectly performed with technical precision for hepatocellular carcinoma (HCC), however, tumor recurrence rates at 5-year remain higher than 70%. Thus, the strategy of hepatectomy needs to be reappraised from insights of scientific aspects. Scientific evidence has suggested that the main causes of recurrence after hepatectomy for HCC are mainly related to underlying cirrhosis and vascular spread of tumor cells that basically cannot be eradicated by hepatectomy. Liver transplant and systemic therapy could be the solution to prevent post-operative recurrence in this regard. Therefore, determining severity of liver cirrhosis for choosing appropriate surgical modalities such as transplant or hepatectomy for HCC and integrating newly emerging immune-related adjuvant or /and neoadjuvant therapy into the strategy of hepatectomy for HCC have become new aspects of exploration to optimize the strategy of hepatectomy. In this new area, hepatectomy for HCC has evolved from a pure technical concept emphasizing on the precision of anatomic resection into a scientific concept emphasizing on an integrated consideration on surgical options, severity of liver cirrhosis, status of vascular invasion and intervention of systemic therapy. By introducing the concept of scientific hepatectomy, the surgical strategy of hepatectomy can be further optimized for individual patients, and survival and recurrent rates can be further improved.