Abstract: : The aim of the current study was to evaluate the effects of dietary supplementation with Nacetylcysteine（NAC）on liver immunological stress and energy status in piglets after lipopolysaccharide (LPS) challenge. Eighteen healthy piglets with the same genetic origin and similar body weight (Duroc ×Landrace × Large white, (11.58 ± 0.26) kg BW) were randomly allocated into 3 treatments (control group, LPS group and NAC group). Each treatment included 6 replicates, one piglet per replicate. The piglets in the control group and LPS group were fed with the basal diet, while the NAC group was fed with the basal diet + 500 mg·kg-1 NAC. On d10, d13 and d20, the piglets in the LPS and NAC groups were injected intraperitoneally with 100 μg·kg-1 BW LPS, and the piglets in the control group were injected intraperitoneally with the same dose of physiological saline. On d10 and d20, blood samples were collected from precava vein after 3 h postinjection of LPS. On d21, all the piglets were sacrificed to collect liver for analysis. The results showed that: (1) Dietary supplementation of NAC attenuated the decrease of F/G （P<0.05）and the increase of ADG（P<0.05）.(2) Dietary supplementation of NAC significantly attenuated the increase of TNFα, IL6 and PGE2 in plasma and liver(P<0.05). (3) Dietary supplementation of NAC attenuated the increase of the expression of NFκB and HSP70 induced by LPS challenge (P<0.05). (4) Dietary supplementation of NAC attenuated the decrease of ATP, ADP and energy charge (EC), while attenuated the increase of AMP level and AMP/ATP induced by LPS challenge significantly (P<0.05). These results indicated, under the present experimental conditions, dietary supplementation with 500 mg·kg-1 NAC could significantly improve growth performance via ameliorating the immunological stress and energy depletion in piglets challenged with LPS.