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The aim of this research was to study the parameters influencing moisture, salt and total phenol content of hot smoked Nile Perch and to compare the influence of processing conditions on its proximate composition and sensory quality. The effect on moisture, salt and total phenol content was investigated using fractional factorial design with seven factors and two levels: X 1 for brine concentration, X 2 for brining time, X 3 for preliminary smoking-drying time, X 4 for smoking time, X 5 for hot smoking time, X 6 for smoking temperature and X 7 for hot smoking temperature. A Multiple Linear Regression Analysis was performed to fit the mathematical model to the collected data and the model tested using analysis of variance (ANOVA). Results of ANOVA indicated the good accuracy and highest significance of the mathematical model. The range of total protein and lipid content was 17.96 to 34.34% and 0.87 to 4.43%, respectively. The range of general acceptability of smoked Nile Perch was 4.6 to 8.2 based on 9-point hedonic scale. Based on the results obtained, including the overall acceptability, proximate composition and smoking criteria of finished product, samples produced with the following conditions: brining at 4% for 270min, drying at 30°C for 30min and the smoked time/ temperature cycles following: 30°C/120min; 50°C/240min and 80°C/240min was the best and most accepted. The results derived from this study indicate that the fractional factorial design is a useful screening tool for improving industrial smoking process of Nile Perch.