An image signal compression method and system. Without involving the current processing pixel, an encryption key and a decryption key are respectively and separately generated by a compression subsystem and a decompression subsystem. Both of the encryption and decryption keys are separately generated using the same principle of pixel prediction. Both of the encryption and decryption keys have the same value. In the compression subsystem, the encryption key is subtracted from the pixel value of the current processing pixel to generate a compressed data. In the decompression subsystem, the decryption key is added to the compressed data to recover the pixel value of the current processing pixel.