In this study, experiments were conducted with four different proportions of seed cake of Karanja (SCK) and cattle dung (CD) mixture, for biogas production. 75, 50 and 25 % of the SCK on a mass basis were mixed with 25, 50 and 75 % of the CD and, named as S 1 , S 2 and S 3 . For comparison, biogas obtained from 100 % CD (S 4 ) was considered. The samples were kept in four different reactors, for 30 days of observation, and the yield of biogas from the samples S 1 , S 2 and S 3 was evaluated. Modeling was carried out for prediction and optimization of biogas production using ANN (artificial neural network) and the GA (genetic algorithm). A multi-layered feed-forward network with hidden neurons and linear output neurons was used for training the network using the input parameters pH, digestion time and C/N ratio for the yield of biogas. The performance of the neural network model was verified, and the correlation coefficients were found to be close to 1, for the samples. The experimental results on the biogas production were validated with the results of the neural network and optimized with the GA. The GA optimized values for pH, digestion time, and the C/N ratio of sample S 3 were found to be 6.68, 14.22 days and 24.1:1, respectively. These optimized data can be used to monitor a large scale anaerobic plant. Among all samples, S 3 gave a better result with respect to the pH, C/N (carbon/nitrogen) ratio, digestion time and biogas yield.