A 4-week study was conducted to determine the effect of starvation on activities and mRNA expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) in hybrid tilapia (Oreochromis niloticus x O. areus). The tissue samples were sampled once a week. Results showed that body weight (BW) and hepatosomatic index (HSI) were decreased significantly (P < 0.05) during starvation. The percentages of crude fat and crude protein in the whole body and the fat content in muscle decreased significantly (P < 0.05), while the rate of moisture and crude ash increased significantly (P < 0.05). The response of LPL, HSL activities and mRNA expression in tissues was tissue dependent. The activities of LPL and HSL in muscle at day 7 were elevated by 2.5 times (P < 0.05) and 11.8 times (P < 0.05) of the value at day 0, respectively, and both then decreased to pre-starvation levels at day 14 and finally stabilized at a certain level afterward. LPL and HSL mRNA abundance in muscle remained relatively stable between 0 and 14 day; then, a significant increase was seen after 14 days. In the liver, LPL activity maintained a significantly increasing trend during starvation, while HSL activity rose dramatically at day 7 of starvation by 2.35 times (P < 0.05) and finally stabilized at a certain level. The mRNA abundance of liver LPL increased significantly during the whole process of starvation (P < 0.05), whereas the mRNA abundance of liver HSL decreased significantly at day 7 of starvation, elevating significantly afterward (P < 0.05).