Abstract Background The performance of previously published glomerular filtration rate (GFR) estimation equations degrades when directly used in Chinese population. We incorporated more independent variables and using complicated non-linear modeling technology (artificial neural network, ANN) to develop a more accurate GFR estimation model for Chinese population. Methods The enrolled participants came from the Third Affiliated Hospital of Sun Yat-sen University, China from Jan 2012 to Jun 2016. Participants with age < 18, unstable kidney function, taking trimethoprim or cimetidine, or receiving dialysis were excluded. Among the finally enrolled 1952 participants, 1075 participants (55.07%) from Jan 2012 to Dec 2014 were assigned as the development data whereas 877 participants (44.93%) from Jan 2015 to Jun 2016 as the internal validation data. We in total developed 3 GFR estimation models: a 4-variable revised CKD-EPI (chronic kidney disease epidemiology collaboration) equation (standardized serum creatinine and cystatin C, age and gender), a 9-variable revised CKD-EPI equation (additional auxiliary variables: body mass index, blood urea nitrogen, albumin, uric acid and hemoglobin), and a 9-variable ANN model. Results Compared with the 4-variable equation, the 9-variable equation could not achieve superior performance in the internal validation data (mean of difference: 5.00 [3.82, 6.54] vs 4.67 [3.55, 5.90], P = 0.5; interquartile range (IQR) of difference: 18.91 [17.43, 20.48] vs 20.11 [18.46, 21.80], P = 0.05; P30: 76.6% [73.7%, 79.5%] vs 75.8% [72.9%, 78.6%], P = 0.4), but the 9-variable ANN model significantly improve bias and P30 accuracy (mean of difference: 2.77 [1.82, 4.10], P = 0.007; IQR: 19.33 [17.77, 21.17], P = 0.3; P30: 80.0% [77.4%, 82.7%], P < 0.001). Conclusions It is suggested that using complicated non-linear models like ANN could fully utilize the predictive ability of the independent variables, and then finally achieve a superior GFR estimation model.