Background Lupus nephritis can be seen in up to 60% of all SLE patients with 10–15% of nephritis patients progressing to end-stage renal disease; late diagnosis of lupus nephritis is correlated with a higher frequency of renal insufficiency. The study aim is determination of the value of urinary human epidermal growth factor (urinary EGF) as an early biomarker of lupus nephritis in SLE patients and its relevance to disease activity and renal histopathology. Results The study included 58 SLE patients and 30 healthy controls; a significant difference was noticed between SLE and controls in urinary protein, creatinine, protein/creatinine ratio, and urinary EGF. The mean level of urinary EGF was less in classes IV and V renal nephritis than in classes I, II, and III. There is a significant difference in urinary EGF (33±29, 27±16, P = 0.04) between class II and class III lupus nephritis, with no significant differences in urinary protein, creatinine, protein/creatinine ratio, and SLEDAI. On the other hand, the comparison between classes II and IV showed significant difference not only in urinary EGF (33±29, 11.7±4.9 m, P=0.003), but also in SLEDAI (37.4±8, 70.5±27, P= 0.007), and protein/creatinine ratio (0.98±0.62, 3±1.8, P=0.006). Conclusion This study raises the attention to test the sensitivity of urinary EGF in detecting the early and the subsequent changes in renal pathology of SLE patients as an easy, non-invasive, accurate, cheap marker that could help in following up the nephritis progression and adjusting the plan of treatment; also, it can be used to guide the time of biopsy or as an alternative in cases where renal biopsy is contraindicated.