This paper summarizes the "study on small hepatocellular carcinoma and its extension" in Liver Cancer Institute, Zhongshan Hospital of Shanghai Medical University during the past 25 years. The results indicated that it was an important approach to obtain long-term HCC survivors, of the 239 patients with 5-year survival, small HCC resection accounted for 51.4%. It was an effective approach to improve the prognosis of HCC in the entire series, the 5-year survival of inpatients treated in authors' institution was 4.8% in 1958-1970, 12.2% in 1971-1983, and 46.7% in 1984-1995; which were correlated to the increase proportion of small HCC resection in the series; it was more effective as compared to large HCC resection, the 5 year survival was 61.3% (n = 645) versus 33.6% (n = 950). Extensions of small HCC study included early detection and treatment of small recurrent HCC, of the 147 patients with re-resection, the 5-year survival was 48.9% calculated from the time of first resection. Another extension was conversion of large HCC into small HCC, using multimodality combination treatment, 72 out of the 663 patients with surgically verified unresectable HCCs have been converted to resectable, 5-year survival being 62.1%, which was comparable to that of small HCC resection. Studies on related basic aspect of small HCC such as cell origin of recurrence, and molecular aspect of small HCC, indicated that biological characteristics, particularly the tumor invasiveness, remained the key link for further prolong survival after small HCC resection. Recently, a "patient-like" human HCC metastatic model in nude mice has been established. Experimental interventions have also been tried. Clinical trials for prevention of recurrence after small HCC resection have shown preliminary encouraging results. However, the "cost-effectiveness" of screening, the invasiveness of HCC, the multicentric origin, the coexisted Child C cirrhosis, etc., remained great challenge.