【Objective】 We undertook to perform a definitive study to describe the diagnostic intervals and the frequent sites of extrahepatic tumors of the patients with multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC) in South China. 【Methods】 Clinical data of 68 MPM patients involving HCC were studied retrospectively to summarize the diagnostic intervals and the frequent sites of extrahepatic tumors. 【Results】 Of the 68 patients in this study

18 developed HCC then other primary cancers (H–O group) and 50 developed other primary cancers then HCC (O-H group). The median diagnostic intervals between the initial and the subsequent tumor was 3 years

respectively (range: 0-18.7 years). No significant difference was observed in the interval time between the O-H and H-O groups (P > 0.50). The EHPMs included nasopharynx

colorectal

lung

skin

gastric

esophagus

cervical

breast

thyroid

oral

urinary bladder

and renal cancer as well as non-Hodgkin lymphoma. The most frequent sites of cancers preceding or following HCC were the following: nasopharynx (11/68

16.2%)

colorectal (10/68

14.7%)

and lung (6/68

8.8%). The most frequent sites in the H-O group were lung

nasopharynx and gastric

and nasopharynx

colorectal and skin in the O–H group.【Conclusion】 A postoperative periodic checkup should be performed intensively especially during the first 5 years. The high site (nasopharynx and gastrointestinal) screening

emphasis on the analysis of the clinical details in low site and the application of the new detection method are of help to the diagnosis of MPM involving HCC.