In summary, we have shown that (1) seven of HCC-derived EGFR mutants (K757E, N808S, R831C, V897A, P937L, T940A, and M947T) identified by our previous study [24] are functioning, EGF-dependent, and erlotinib-resistant; (2) erlotinib induces differential degree of apoptosis and autophagy among cells harboring different EGFRs mutants; (3) the degree of inhibition of EGFR phosphorylation by erlotinib is the determining factor for the degree of apoptosis and autophagy amongst cells harboring EGFR mutants. The gene discussed is EGFR; the disease is hepatocellular carcinoma.