Predicting a variable using other variables in a large data set is a very difficult task. It involves selecting variables to include in a model and determining the shape of the relationship between variables. Nonparametric regression such as smoothing splines and neural networks are widely-used methods for such a task. We propose an alternative method based on a genetic algorithm(GA) to solve this problem. We applied GA to regression splines, a nonparametric regression method, to estimate functional forms between variables. Using several simulated and real data, our technique is shown to outperform traditional nonparametric methods such as smoothing splines and neural networks.