In order to create a practical road-resistance function for work zones under different lane occupation conditions, the expected speed of vehicles was calibrated in the work zone simulation model based on measured data, and simulation models were constructed for the closed half lane and the closed inside lane under different rates of trucks. Based on the statistical theory, the influence of significance of traffic volume and truck ratios for road resistance was analyzed, and a suitable truck ratio was found for the work zone. By using the optimal nonlinear fitting theory, the practical road-resistance function for work zones under different lane occupation conditions was constructed. The results showed that the road resistance is significantly affected by the traffic volume and rate of trucks. Under the same truck ratio, the road resistance linearly increases slowly when the traffic volume is less than the critical traffic volume and rapid increases irregularly when it is greater than the critical traffic volume. Under the same traffic load, the road resistance of the work zone increases with the increase in the rate of trucks, and the difference is not obvious when the traffic volume is less than the critical traffic volume, and increases gradually when it is greater than the critical traffic volume. Through the goodness of fit test and the homogeneity of variance test, the road-resistance function constructed in this paper has high goodness of fit. The practical road-resistance functions constructed in this study could be used to guide the diversion of the rebuilt/expanded highway to ensure traffic safety. Further, the study provides a theoretical basis for the construction of intelligent highway work zones.