This study was conducted to evaluate the effects of E-liquids that contain or free nicotine on blood physiological and biochemical parameters during the stages of chemically induced rat liver carcinogenesis after intraperitoneal injection of Diethylnitrosamine (DEN). 10 weeks old, male Sprague Dawley (S.D.) rats weighing 120 - 125 grams, were split into 4 groups: G1 (-ve control), G2 (DEN only), G3 (DEN + Nicotine-free e-liquid, 0.5 mg/kg of body weight), and G4 (DEN + E-liquid with nicotine, 0.5 mg/kg of body weight). After 32 weeks of experimentation, rats were killed. Blood samples in G4 showed increased ALT, decreased AST, and platelet counts. Kidney function levels were significantly increased after both E-liquids containing nicotine with higher levels. Moreover, E-liquids dramatically increased the triglycerides and decreased the HDL levels. Additionally, the blood glucose and serum electrolyte levels were markedly elevated by E-liquid with nicotine other than that without nicotine. In conclusion, the E-liquid with nicotine exerted a deleterious effect on blood parameters during liver carcinogenesis.