Storage via freezing remains the most effective approach for fish preservation. However, lipid oxidation and protein denaturation still occur during storage, along with nutritional loss. The extent of lipid alteration and protein denaturation are associated with human health defects. To precisely predict common carp (Cyprinus carpio) nutritional quality change during frozen storage, here, we first determined lipid oxidation and hydrolysis and protein denaturation of common carp fillets during 17 weeks of frozen preservation at 261 K, 253 K, and 245 K. Results showed that the content of thiobarbituric acid reactive substances (TBARS) and free fatty acids (FFA) were significantly increased. However, salt-soluble protein (SSP) content, Ca2+-ATPase activity, and total sulfhydryl (SH) content kept decreasing during frozen storage, with SSP content decreasing by 64.82%, 38.14%, and 11.24%, respectively, Ca2+-ATP enzyme activity decreasing to 12.50%, 18.52%, and 28.57% Piμmol/mg/min, and SH values decreasing by 70.71%, 64.92%, and 56.51% at 261 K, 253 K, and 245 K, respectively. The values at 261 K decreased more than that at 253 K and 245 K (p < 0.05). Ca2+-ATPase activity was positively correlated (r = 0.96) with SH content. Afterwards, based on the results of the above chemical experiments, we developed a radial basis function neural network (RBFNN) to predict the modification of lipid and protein of common carp fillets during frozen storage. Results showed that all the relative errors of experimental and predicted values were within ±10%. In summary, the quality of common carp can be well protected at 245 K, and the established RBFNN could effectively predict the quality of the common carp under frozen conditions at 261–245 K.