A Quantum Stream Cipher (QSC) using Quadrature Amplitude Modulation (QAM) is presented to greatly increase the secure degree compared with ASK or PSK/QSC. We propose encoding multi-bit data in one symbol with a multi-bit basis state, resulting in QAM/QSC, which employs amplitude and phase encryption of the light beam simultaneously. A 16 QAM/QSC experiment at 10 Gbit/s was successfully carried out over 160 km using a digital coherent optical transmission technique, where 16 QAM data were encrypted in a constellation with 32 × 32~4096 × 4096 symbols. We show experimentally that the Number of Masked Signals (NMS) in the quantum noise Γ(QAM) for QAM/QSC becomes a square multiple larger than Γ(ASK) for ASK/QSC. Γ(QAM) exceeds 10,000. This result indicates that the QSC technique is more robust against eavesdroppers than ASK or PSK/QSC.