Hepatocellular　carcinoma　(HCC)　is　one　of　the　most　common　malignant　tumors.　Traditional　chemotherapy　drugs　are　hard　to　reach　a　satisfactory　therapeutic　effect　since　advanced　HCC　is　highly　chemoresistant.　Sorafenib　is　an　oral　multikinase　inhibitor　that　can　suppress　tumor　cell　proliferation,　angiogenesis　and　induce　cancer　cell　apoptosis.　However,　the　poor　solubility,　rapid　metabolism　and　low　bioavailability　of　sorafenib　greatly　restricted　its　further　clinical　application.　During　the　past　decade,　numerous　sorafenib　derivatives　have　been　designed　and　synthesized　to　overcome　its　disadvantages　and　improve　its　clinical　performance.　This　article　focuses　on　the　therapeutic　effects　and　mechanisms　of　various　sorafenib　derivatives　with　modifications　on　the　N-methylpicolinamide　group,　urea　group,　central　aromatic　ring　or　others.　More　importantly,　this　review　summarizes　the　current　status　of　the　structure-activity　relationship　(SAR)　of　reported　sorafenib　derivatives,　which　can　provide　some　detailed　information　of　future　directions　for　further　structural　modifications　of　sorafenib　to　discovery　new　anti-tumor　drugs　with　improved　clinical　performance.　(C)　2019　Elsevier　Masson　SAS.　All　rights　reserved.